Skip to main content
Top
Published in: Brain Structure and Function 5/2014

01-09-2014 | Original Article

Impact of a multi-nutrient diet on cognition, brain metabolism, hemodynamics, and plasticity in apoE4 carrier and apoE knockout mice

Authors: Diane Jansen, Valerio Zerbi, Carola I. F. Janssen, Daan van Rooij, Bastian Zinnhardt, Pieter J. Dederen, Alan J. Wright, Laus M. Broersen, Dieter Lütjohann, Arend Heerschap, Amanda J. Kiliaan

Published in: Brain Structure and Function | Issue 5/2014

Login to get access

Abstract

Lipid metabolism and genetic background together strongly influence the development of both cardiovascular and neurodegenerative diseases like Alzheimer’s disease (AD). A non-pharmacological way to prevent the genotype-induced occurrence of these pathologies is given by dietary behavior. In the present study, we tested the effects of long-term consumption of a specific multi-nutrient diet in two models for atherosclerosis and vascular risk factors in AD: the apolipoprotein ε4 (apoE4) and the apoE knockout (apoE ko) mice. This specific multi-nutrient diet was developed to support neuronal membrane synthesis and was expected to contribute to the maintenance of vascular health. At 12 months of age, both genotypes showed behavioral changes compared to control mice and we found increased neurogenesis in apoE ko mice. The specific multi-nutrient diet decreased anxiety-related behavior in the open field, influenced sterol composition in serum and brain tissue, and increased the concentration of omega-3 fatty acids in the brain. Furthermore, we found that wild-type and apoE ko mice fed with this multi-nutrient diet showed locally increased cerebral blood volume and decreased hippocampal glutamate levels. Taken together, these data suggest that a specific dietary intervention has beneficial effects on early pathological consequences of hypercholesterolemia and vascular risk factors for AD.
Literature
go back to reference Arendash GW, Jensen MT, Salem N Jr, Hussein N, Cracchiolo J, Dickson A, Leighty R, Potter H (2007) A diet high in omega-3 fatty acids does not improve or protect cognitive performance in Alzheimer’s transgenic mice. Neuroscience 149(2):286–302PubMed Arendash GW, Jensen MT, Salem N Jr, Hussein N, Cracchiolo J, Dickson A, Leighty R, Potter H (2007) A diet high in omega-3 fatty acids does not improve or protect cognitive performance in Alzheimer’s transgenic mice. Neuroscience 149(2):286–302PubMed
go back to reference Arendt T (2001) Alzheimer’s disease as a disorder of mechanisms underlying structural brain self-organization. Neuroscience 102(4):723–765PubMed Arendt T (2001) Alzheimer’s disease as a disorder of mechanisms underlying structural brain self-organization. Neuroscience 102(4):723–765PubMed
go back to reference Artham SM, Lavie CJ, Milani RV, Anand RG, O’Keefe JH, Ventura HO (2008) Fish oil in primary and secondary cardiovascular prevention. Ochsner J 8(2):49–60PubMedCentralPubMed Artham SM, Lavie CJ, Milani RV, Anand RG, O’Keefe JH, Ventura HO (2008) Fish oil in primary and secondary cardiovascular prevention. Ochsner J 8(2):49–60PubMedCentralPubMed
go back to reference Ashburner J, Friston KJ (2000) Voxel-based morphometry—the methods. NeuroImage 11(6 Pt 1):805–821PubMed Ashburner J, Friston KJ (2000) Voxel-based morphometry—the methods. NeuroImage 11(6 Pt 1):805–821PubMed
go back to reference Avants BB, Epstein CL, Grossman M, Gee JC (2008) Symmetric diffeomorphic image registration with cross-correlation: evaluating automated labeling of elderly and neurodegenerative brain. Med Image Anal 12(1):26–41PubMedCentralPubMed Avants BB, Epstein CL, Grossman M, Gee JC (2008) Symmetric diffeomorphic image registration with cross-correlation: evaluating automated labeling of elderly and neurodegenerative brain. Med Image Anal 12(1):26–41PubMedCentralPubMed
go back to reference Barberger-Gateau P, Samieri C, Feart C, Plourde M (2011) Dietary omega 3 polyunsaturated fatty acids and Alzheimer’s disease: interaction with apolipoprotein E genotype. Curr Alzheimer Res 8(5):479–491PubMedCentralPubMed Barberger-Gateau P, Samieri C, Feart C, Plourde M (2011) Dietary omega 3 polyunsaturated fatty acids and Alzheimer’s disease: interaction with apolipoprotein E genotype. Curr Alzheimer Res 8(5):479–491PubMedCentralPubMed
go back to reference Bell RD, Winkler EA, Singh I, Sagare AP, Deane R, Wu Z, Holtzman DM, Betsholtz C, Armulik A, Sallstrom J, Berk BC, Zlokovic BV (2012) Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 485(7399):512–516. doi:10.1038/nature11087 PubMedCentralPubMed Bell RD, Winkler EA, Singh I, Sagare AP, Deane R, Wu Z, Holtzman DM, Betsholtz C, Armulik A, Sallstrom J, Berk BC, Zlokovic BV (2012) Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 485(7399):512–516. doi:10.​1038/​nature11087 PubMedCentralPubMed
go back to reference Belliveau JW, Rosen BR, Kantor HL, Rzedzian RR, Kennedy DN, McKinstry RC, Vevea JM, Cohen MS, Pykett IL, Brady TJ (1990) Functional cerebral imaging by susceptibility-contrast NMR. Magn Reson Med 14(3):538–546PubMed Belliveau JW, Rosen BR, Kantor HL, Rzedzian RR, Kennedy DN, McKinstry RC, Vevea JM, Cohen MS, Pykett IL, Brady TJ (1990) Functional cerebral imaging by susceptibility-contrast NMR. Magn Reson Med 14(3):538–546PubMed
go back to reference Boekhoorn K, Joels M, Lucassen PJ (2006) Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus. Neurobiol Dis 24(1):1–14. doi:10.1016/j.nbd.2006.04.017 PubMed Boekhoorn K, Joels M, Lucassen PJ (2006) Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus. Neurobiol Dis 24(1):1–14. doi:10.​1016/​j.​nbd.​2006.​04.​017 PubMed
go back to reference Bour A, Grootendorst J, Vogel E, Kelche C, Dodart JC, Bales K, Moreau PH, Sullivan PM, Mathis C (2008) Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks. Behav Brain Res 193(2):174–182PubMed Bour A, Grootendorst J, Vogel E, Kelche C, Dodart JC, Bales K, Moreau PH, Sullivan PM, Mathis C (2008) Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks. Behav Brain Res 193(2):174–182PubMed
go back to reference Bourre JM, Francois M, Youyou A, Dumont O, Piciotti M, Pascal G, Durand G (1989) The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. J Nutr 119(12):1880–1892PubMed Bourre JM, Francois M, Youyou A, Dumont O, Piciotti M, Pascal G, Durand G (1989) The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. J Nutr 119(12):1880–1892PubMed
go back to reference Bourre JM, Dumont O, Piciotti M, Clement M, Chaudiere J, Bonneil M, Nalbone G, Lafont H, Pascal G, Durand G (1991) Essentiality of omega 3 fatty acids for brain structure and function. World Rev Nutr Diet 66:103–117PubMed Bourre JM, Dumont O, Piciotti M, Clement M, Chaudiere J, Bonneil M, Nalbone G, Lafont H, Pascal G, Durand G (1991) Essentiality of omega 3 fatty acids for brain structure and function. World Rev Nutr Diet 66:103–117PubMed
go back to reference Boxerman JL, Hamberg LM, Rosen BR, Weisskoff RM (1995) MR contrast due to intravascular magnetic susceptibility perturbations. Magn Reson Med 34(4):555–566PubMed Boxerman JL, Hamberg LM, Rosen BR, Weisskoff RM (1995) MR contrast due to intravascular magnetic susceptibility perturbations. Magn Reson Med 34(4):555–566PubMed
go back to reference Breslow JL (1996) Mouse models of atherosclerosis. Science 272(5265):658–688 Breslow JL (1996) Mouse models of atherosclerosis. Science 272(5265):658–688
go back to reference Breteler MM (2000) Vascular risk factors for Alzheimer’s disease: an epidemiologic perspective. Neurobiol Aging 21(2):153–160PubMed Breteler MM (2000) Vascular risk factors for Alzheimer’s disease: an epidemiologic perspective. Neurobiol Aging 21(2):153–160PubMed
go back to reference Calder PC (2001) Polyunsaturated fatty acids, inflammation, and immunity. Lipids 36(9):1007–1024PubMed Calder PC (2001) Polyunsaturated fatty acids, inflammation, and immunity. Lipids 36(9):1007–1024PubMed
go back to reference Carrie I, Smirnova M, Clement M, De JD, Frances H, Bourre JM (2002) Docosahexaenoic acid-rich phospholipid supplementation: effect on behavior, learning ability, and retinal function in control and n-3 polyunsaturated fatty acid deficient old mice. Nutr Neurosci 5(1):43–52PubMed Carrie I, Smirnova M, Clement M, De JD, Frances H, Bourre JM (2002) Docosahexaenoic acid-rich phospholipid supplementation: effect on behavior, learning ability, and retinal function in control and n-3 polyunsaturated fatty acid deficient old mice. Nutr Neurosci 5(1):43–52PubMed
go back to reference Caselli RJ, Graff-Radford NR, Reiman EM, Weaver A, Osborne D, Lucas J, Uecker A, Thibodeau SN (1999) Preclinical memory decline in cognitively normal apolipoprotein E-epsilon4 homozygotes. Neurology 53(1):201–207PubMed Caselli RJ, Graff-Radford NR, Reiman EM, Weaver A, Osborne D, Lucas J, Uecker A, Thibodeau SN (1999) Preclinical memory decline in cognitively normal apolipoprotein E-epsilon4 homozygotes. Neurology 53(1):201–207PubMed
go back to reference Cavassila S, Deval S, Huegen C, van Ormondt D, Graveron-Demilly D (2001) Cramer-Rao bounds: an evaluation tool for quantitation. NMR Biomed 14(4):278–283PubMed Cavassila S, Deval S, Huegen C, van Ormondt D, Graveron-Demilly D (2001) Cramer-Rao bounds: an evaluation tool for quantitation. NMR Biomed 14(4):278–283PubMed
go back to reference Chen PE, Specht CG, Morris RGM, Schoepfer R (2002) Spatial learning is unimpaired in mice containing a deletion of the alpha-synuclein locus. Eur J Neurosci 16(1):154–158PubMed Chen PE, Specht CG, Morris RGM, Schoepfer R (2002) Spatial learning is unimpaired in mice containing a deletion of the alpha-synuclein locus. Eur J Neurosci 16(1):154–158PubMed
go back to reference Chiu CC, Su KP, Cheng TC, Liu HC, Chang CJ, Dewey ME, Stewart R, Huang SY (2008) The effects of omega-3 fatty acids monotherapy in Alzheimer’s disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry 32(6):1538–1544. doi:10.1016/j.pnpbp.2008.05.015 PubMed Chiu CC, Su KP, Cheng TC, Liu HC, Chang CJ, Dewey ME, Stewart R, Huang SY (2008) The effects of omega-3 fatty acids monotherapy in Alzheimer’s disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry 32(6):1538–1544. doi:10.​1016/​j.​pnpbp.​2008.​05.​015 PubMed
go back to reference Claassen V (1994) Neglected factors in pharmacology and neuroscience research: focus on : biopharmaceutics, animal characteristics, maintenance, testing conditions. Elsevier, Amsterdam Claassen V (1994) Neglected factors in pharmacology and neuroscience research: focus on : biopharmaceutics, animal characteristics, maintenance, testing conditions. Elsevier, Amsterdam
go back to reference Cole GM, Frautschy SA (2006) Docosahexaenoic acid protects from amyloid and dendritic pathology in an Alzheimer’s disease mouse model. Nutr Health (Berkhamsted, Hertfordshire) 18(3):249–259 Cole GM, Frautschy SA (2006) Docosahexaenoic acid protects from amyloid and dendritic pathology in an Alzheimer’s disease mouse model. Nutr Health (Berkhamsted, Hertfordshire) 18(3):249–259
go back to reference Cole GM, Ma QL, Frautschy SA (2009) Omega-3 fatty acids and dementa. Prostaglandins Leukot Essent Fatty Acids 81(2–3):213–221 Cole GM, Ma QL, Frautschy SA (2009) Omega-3 fatty acids and dementa. Prostaglandins Leukot Essent Fatty Acids 81(2–3):213–221
go back to reference Conte V, Uryu K, Fujimoto S, Yao Y, Rokach J, Longhi L, Trojanowski JQ, Lee VM, McIntosh TK, Praticò D (2004) Vitamin E reducs amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury. J Neurochem 90(3):758–764PubMed Conte V, Uryu K, Fujimoto S, Yao Y, Rokach J, Longhi L, Trojanowski JQ, Lee VM, McIntosh TK, Praticò D (2004) Vitamin E reducs amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury. J Neurochem 90(3):758–764PubMed
go back to reference Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261(5123):921–923 Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261(5123):921–923
go back to reference Crupi R, Cambiaghi M, Deckelbaum R, Hansen I, Mindes J, Spina E, Battaglia F (2012) n-3 fatty acids prevent impairment of neurogenesis and synaptic plasticity in B-cell activating factor (BAFF) transgenic mice. Prevent Med 54(Suppl):S103–S108. doi:10.1016/j.ypmed.2011.12.019 Crupi R, Cambiaghi M, Deckelbaum R, Hansen I, Mindes J, Spina E, Battaglia F (2012) n-3 fatty acids prevent impairment of neurogenesis and synaptic plasticity in B-cell activating factor (BAFF) transgenic mice. Prevent Med 54(Suppl):S103–S108. doi:10.​1016/​j.​ypmed.​2011.​12.​019
go back to reference Cuppini R, Ciaroni S, Cecchini T, Ambrogini P, Ferri P, Cuppini C, Ninfali P, Del Grande P (2002) Tocopherols enhance neurogenesis in dentate gyrus of adult rats. Int J Vitam Nutr Res (Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung Journal international de vitaminologie et de nutrition) 72(3):170–176 Cuppini R, Ciaroni S, Cecchini T, Ambrogini P, Ferri P, Cuppini C, Ninfali P, Del Grande P (2002) Tocopherols enhance neurogenesis in dentate gyrus of adult rats. Int J Vitam Nutr Res (Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung Journal international de vitaminologie et de nutrition) 72(3):170–176
go back to reference Curtis MA, Penney EB, Pearson AG, van Roon-Mom WM, Butterworth NJ, Dragunow M, Connor B, Faull RL (2003) Increased cell proliferation and neurogenesis in the adult human Huntington’s disease brain. Proc Natl Acad Sci USA 100(15):9023–9027. doi:10.1073/pnas.1532244100 PubMedCentralPubMed Curtis MA, Penney EB, Pearson AG, van Roon-Mom WM, Butterworth NJ, Dragunow M, Connor B, Faull RL (2003) Increased cell proliferation and neurogenesis in the adult human Huntington’s disease brain. Proc Natl Acad Sci USA 100(15):9023–9027. doi:10.​1073/​pnas.​1532244100 PubMedCentralPubMed
go back to reference Dangour AD, Allen E, Elbourne D, Fasey N, Fletcher AE, Hardy P, Holder GE, Knight R, Letley L, Richards M, Uauy R (2010) Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial. Am J Clin Nutr 91(6):1725–1732. doi:10.3945/ajcn.2009.29121 PubMed Dangour AD, Allen E, Elbourne D, Fasey N, Fletcher AE, Hardy P, Holder GE, Knight R, Letley L, Richards M, Uauy R (2010) Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial. Am J Clin Nutr 91(6):1725–1732. doi:10.​3945/​ajcn.​2009.​29121 PubMed
go back to reference Das UN (2008) Folic acid and polyunsaturated fatty acids improve cognitive function and prevent depression, dementia, and Alzheimer’s disease–but how and why? Prostaglandins Leukot Essent Fatty Acids 78(1):11–19. doi:10.1016/j.plefa.2007.10.006 PubMed Das UN (2008) Folic acid and polyunsaturated fatty acids improve cognitive function and prevent depression, dementia, and Alzheimer’s disease–but how and why? Prostaglandins Leukot Essent Fatty Acids 78(1):11–19. doi:10.​1016/​j.​plefa.​2007.​10.​006 PubMed
go back to reference Davignon J (2005) Apolipoprotein E and atherosclerosis: beyond lipid effect. Arterioscler Thromb Vasc Biol 25(2):267–269PubMed Davignon J (2005) Apolipoprotein E and atherosclerosis: beyond lipid effect. Arterioscler Thromb Vasc Biol 25(2):267–269PubMed
go back to reference Davignon J, Gregg RE, Sing CF (1988) Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 8(1):1–21 Davignon J, Gregg RE, Sing CF (1988) Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 8(1):1–21
go back to reference de Bruin JP, Sanchez-Santed F, Heinsbroek RP, Donker A, Postmes P (1994) A behavioural analysis of rats with damage to the medial prefrontal cortex using the Morris water maze: evidence for behavioural flexibility, but not for impaired spatial navigation. Brain Res 652(2):323–333PubMed de Bruin JP, Sanchez-Santed F, Heinsbroek RP, Donker A, Postmes P (1994) A behavioural analysis of rats with damage to the medial prefrontal cortex using the Morris water maze: evidence for behavioural flexibility, but not for impaired spatial navigation. Brain Res 652(2):323–333PubMed
go back to reference De Bruin NM, Kiliaan AJ, De Wilde MC, Broersen LM (2003) Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats. Neurobiol Learn Mem 80(1):63–79PubMed De Bruin NM, Kiliaan AJ, De Wilde MC, Broersen LM (2003) Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats. Neurobiol Learn Mem 80(1):63–79PubMed
go back to reference DeKosky ST, Scheff SW, Styren SD (1996) Structural correlates of cognition in dementia: quantification and assessment of synapse change. Neurodegeneration 5(4):417–421PubMed DeKosky ST, Scheff SW, Styren SD (1996) Structural correlates of cognition in dementia: quantification and assessment of synapse change. Neurodegeneration 5(4):417–421PubMed
go back to reference Dennie J, Mandeville JB, Boxerman JL, Packard SD, Rosen BR, Weisskoff RM (1998) NMR imaging of changes in vascular morphology due to tumor angiogenesis. Magn Reson Med 40(6):793–799PubMed Dennie J, Mandeville JB, Boxerman JL, Packard SD, Rosen BR, Weisskoff RM (1998) NMR imaging of changes in vascular morphology due to tumor angiogenesis. Magn Reson Med 40(6):793–799PubMed
go back to reference Dong H, Martin MV, Chambers S, Csernansky JG (2007) Spatial relationship between synapse loss and beta-amyloid deposition in Tg2576 mice. J Comp Neurol 500(2):311–321PubMedCentralPubMed Dong H, Martin MV, Chambers S, Csernansky JG (2007) Spatial relationship between synapse loss and beta-amyloid deposition in Tg2576 mice. J Comp Neurol 500(2):311–321PubMedCentralPubMed
go back to reference Dyall SC, Michael GJ, Michael-Titus AT (2010) Omega-3 fatty acids reverse age-related decreases in nuclear receptors and increase neurogenesis in old rats. J Neurosci Res 88(10):2091–2102. doi:10.1002/jnr.22390 PubMed Dyall SC, Michael GJ, Michael-Titus AT (2010) Omega-3 fatty acids reverse age-related decreases in nuclear receptors and increase neurogenesis in old rats. J Neurosci Res 88(10):2091–2102. doi:10.​1002/​jnr.​22390 PubMed
go back to reference Ercan M, Koksal C, Konukoglu D, Bozkurt AK, Onen S (2003) Impaired plasma viscosity via increased cholesterol levels in peripheral occlusive arterial disease [correction of disase]. Clin Hemorheol Microcirc 29(1):3–9PubMed Ercan M, Koksal C, Konukoglu D, Bozkurt AK, Onen S (2003) Impaired plasma viscosity via increased cholesterol levels in peripheral occlusive arterial disease [correction of disase]. Clin Hemorheol Microcirc 29(1):3–9PubMed
go back to reference Farkas E, de Wilde MC, Kiliaan AJ, Meijer J, Keijser JN, Luiten PG (2002) Dietary long chain PUFAs differentially affect hippocampal muscarinic 1 and serotonergic 1A receptors in experimental cerebral hypoperfusion. Brain Res 954(1):32–41PubMed Farkas E, de Wilde MC, Kiliaan AJ, Meijer J, Keijser JN, Luiten PG (2002) Dietary long chain PUFAs differentially affect hippocampal muscarinic 1 and serotonergic 1A receptors in experimental cerebral hypoperfusion. Brain Res 954(1):32–41PubMed
go back to reference Fedorova I, Salem N Jr (2006) Omega-3 fatty acids and rodent behavior. Prostaglandins Leukot Essent Fatty Acids 75(4–5):271–289PubMed Fedorova I, Salem N Jr (2006) Omega-3 fatty acids and rodent behavior. Prostaglandins Leukot Essent Fatty Acids 75(4–5):271–289PubMed
go back to reference Ferretti L, McCurry SM, Logsdon R, Gibbons L, Teri L (2001) Anxiety and Alzheimer’s disease. J Geriatr Psychiatry Neurol 14(1):52–58PubMed Ferretti L, McCurry SM, Logsdon R, Gibbons L, Teri L (2001) Anxiety and Alzheimer’s disease. J Geriatr Psychiatry Neurol 14(1):52–58PubMed
go back to reference Fontani G, Corradeschi F, Felici A, Alfatti F, Migliorini S, Lodi L (2005) Cognitive and physiological effects of Omega-3 polyunsaturated fatty acid supplementation in healthy subjects. Eur J Clin Invest 35(11):691–699PubMed Fontani G, Corradeschi F, Felici A, Alfatti F, Migliorini S, Lodi L (2005) Cognitive and physiological effects of Omega-3 polyunsaturated fatty acid supplementation in healthy subjects. Eur J Clin Invest 35(11):691–699PubMed
go back to reference Francis F, Koulakoff A, Boucher D, Chafey P, Schaar B, Vinet MC, Friocourt G, McDonnell N, Reiner O, Kahn A, McConnell SK, Berwald-Netter Y, Denoulet P, Chelly J (1999) Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron 23(2):247–256PubMed Francis F, Koulakoff A, Boucher D, Chafey P, Schaar B, Vinet MC, Friocourt G, McDonnell N, Reiner O, Kahn A, McConnell SK, Berwald-Netter Y, Denoulet P, Chelly J (1999) Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron 23(2):247–256PubMed
go back to reference Franklin KBJ, Paxinos G (1997) The mouse brain in stereotaxic coordinates. Academic Press, San Diego Franklin KBJ, Paxinos G (1997) The mouse brain in stereotaxic coordinates. Academic Press, San Diego
go back to reference Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J (2006) Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol 63(10):1402–1408PubMed Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J (2006) Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol 63(10):1402–1408PubMed
go back to reference Freund-Levi Y, Basun H, Cederholm T, Faxen-Irving G, Garlind A, Grut M, Vedin I, Palmblad J, Wahlund LO, Eriksdotter-Jonhagen M (2008) Omega-3 supplementation in mild to moderate Alzheimer’s disease: effects on neuropsychiatric symptoms. Int J Geriatr Psychiatry 23(2):161–169. doi:10.1002/gps.1857 PubMed Freund-Levi Y, Basun H, Cederholm T, Faxen-Irving G, Garlind A, Grut M, Vedin I, Palmblad J, Wahlund LO, Eriksdotter-Jonhagen M (2008) Omega-3 supplementation in mild to moderate Alzheimer’s disease: effects on neuropsychiatric symptoms. Int J Geriatr Psychiatry 23(2):161–169. doi:10.​1002/​gps.​1857 PubMed
go back to reference Fujii A, Matsumoto H, Yamamoto H (1996) Effect of vitamin B complex on neurotransmission and neurite outgrowth. Gen Pharmacol 27(6):995–1000PubMed Fujii A, Matsumoto H, Yamamoto H (1996) Effect of vitamin B complex on neurotransmission and neurite outgrowth. Gen Pharmacol 27(6):995–1000PubMed
go back to reference Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ (2002) Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. J Hypertens 20(8):1493–1499PubMed Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ (2002) Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. J Hypertens 20(8):1493–1499PubMed
go back to reference Gleeson JG, Lin PT, Flanagan LA, Walsh CA (1999) Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 23(2):257–271PubMed Gleeson JG, Lin PT, Flanagan LA, Walsh CA (1999) Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 23(2):257–271PubMed
go back to reference Goodfellow J, Bellamy MF, Ramsey MW, Jones CJ, Lewis MJ (2000) Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia. J Am Coll Cardiol 35(2):265–270PubMed Goodfellow J, Bellamy MF, Ramsey MW, Jones CJ, Lewis MJ (2000) Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia. J Am Coll Cardiol 35(2):265–270PubMed
go back to reference Gordon I, Grauer E, Genis I, Sehayek E, Michaelson DM (1995) Memory deficits and cholinergic impairments in apolipoprotein E-deficient mice. Neurosci Lett 199(1):1–4PubMed Gordon I, Grauer E, Genis I, Sehayek E, Michaelson DM (1995) Memory deficits and cholinergic impairments in apolipoprotein E-deficient mice. Neurosci Lett 199(1):1–4PubMed
go back to reference Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ (1999) Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci 2(3):260–265. doi:10.1038/6365 PubMed Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ (1999) Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci 2(3):260–265. doi:10.​1038/​6365 PubMed
go back to reference Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS, Thompson LM, LaFerla FM (2008) Nicotinamide restores cognition in Alzheimer’s disease transgenic mice via a mechanisms involving sirtuin inhibition and selective reduction of Thr231-phosphotau. J Neurosci 28(45):11500–11510PubMedCentralPubMed Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS, Thompson LM, LaFerla FM (2008) Nicotinamide restores cognition in Alzheimer’s disease transgenic mice via a mechanisms involving sirtuin inhibition and selective reduction of Thr231-phosphotau. J Neurosci 28(45):11500–11510PubMedCentralPubMed
go back to reference Greenberg DA, Jin K (2006) Neurodegeneration and neurogenesis: focus on Alzheimer’s disease. Curr Alzheimer Res 3(1):25–28PubMed Greenberg DA, Jin K (2006) Neurodegeneration and neurogenesis: focus on Alzheimer’s disease. Curr Alzheimer Res 3(1):25–28PubMed
go back to reference Grootendorst J, de Kloet ER, Dalm S, Oitzl MS (2001a) Reversal of cognitive deficit of apolipoprotein E knockout mice after repeated exposure to a common environmental experience. Neuroscience 108(2):237–247PubMed Grootendorst J, de Kloet ER, Dalm S, Oitzl MS (2001a) Reversal of cognitive deficit of apolipoprotein E knockout mice after repeated exposure to a common environmental experience. Neuroscience 108(2):237–247PubMed
go back to reference Grootendorst J, de Kloet ER, Vossen C, Dalm S, Oitzl MS (2001b) Repeated exposure to rats has persistent genotype-dependent effects on learning and locomotor activity of apolipoprotein E knockout and C57Bl/6 mice. Behav Brain Res 125(1–2):249–259PubMed Grootendorst J, de Kloet ER, Vossen C, Dalm S, Oitzl MS (2001b) Repeated exposure to rats has persistent genotype-dependent effects on learning and locomotor activity of apolipoprotein E knockout and C57Bl/6 mice. Behav Brain Res 125(1–2):249–259PubMed
go back to reference Grootendorst J, Kempes MM, Lucassen PJ, Dalm S, de Kloet ER, Oitzl MS (2002) Differential effect of corticosterone on spatial learning abilities in apolipoprotein E knockout and C57BL/6J mice. Brain Res 953(1–2):281–285PubMed Grootendorst J, Kempes MM, Lucassen PJ, Dalm S, de Kloet ER, Oitzl MS (2002) Differential effect of corticosterone on spatial learning abilities in apolipoprotein E knockout and C57BL/6J mice. Brain Res 953(1–2):281–285PubMed
go back to reference Grootendorst J, Bour A, Vogel E, Kelche C, Sullivan PM, Dodart JC, Bales K, Mathis C (2005) Human apoE targeted replacement mouse lines: h-apoE4 and h-apoE3 mice differ on spatial memory performance and avoidance behavior. Behav Brain Res 159(1):1–14. doi:10.1016/j.bbr.2004.09.019 PubMed Grootendorst J, Bour A, Vogel E, Kelche C, Sullivan PM, Dodart JC, Bales K, Mathis C (2005) Human apoE targeted replacement mouse lines: h-apoE4 and h-apoE3 mice differ on spatial memory performance and avoidance behavior. Behav Brain Res 159(1):1–14. doi:10.​1016/​j.​bbr.​2004.​09.​019 PubMed
go back to reference Grossberg GT (2003) Diagnosis and treatment of Alzheimer’s disease. J Clin Psychiatry 64(Suppl 9):3–6PubMed Grossberg GT (2003) Diagnosis and treatment of Alzheimer’s disease. J Clin Psychiatry 64(Suppl 9):3–6PubMed
go back to reference Guerrero AL, Dorado-Martinez C, Rodriguez A, Pedroza-Rios K, Borgonio-Perez G, Rivas-Arancibia S (1999) Effects of vitamin E on ozone-induced memory deficits and lipid peroxidation in rats. NeuroReport 10(8):1689–1692PubMed Guerrero AL, Dorado-Martinez C, Rodriguez A, Pedroza-Rios K, Borgonio-Perez G, Rivas-Arancibia S (1999) Effects of vitamin E on ozone-induced memory deficits and lipid peroxidation in rats. NeuroReport 10(8):1689–1692PubMed
go back to reference Gupta A, Guyomard V, Zaman MJ, Rehman HU, Myint PK (2010) Systematic review on evidence of the effectiveness of cholesterol-lowering drugs. Adv Therapy 27(6):348–364. doi:10.1007/s12325-010-0033-6 Gupta A, Guyomard V, Zaman MJ, Rehman HU, Myint PK (2010) Systematic review on evidence of the effectiveness of cholesterol-lowering drugs. Adv Therapy 27(6):348–364. doi:10.​1007/​s12325-010-0033-6
go back to reference Gureviciene I, Gurevicius K, Tanila H (2007) Role of alpha-synuclein in synaptic glutamate release. Neurobiol Dis 28(1):83–89PubMed Gureviciene I, Gurevicius K, Tanila H (2007) Role of alpha-synuclein in synaptic glutamate release. Neurobiol Dis 28(1):83–89PubMed
go back to reference Haag MD, Hofman A, Koudstaal PJ, Stricker BH, Breteler MM (2009) Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study. J Neurol Neurosurg Psychiatry 80(1):13–17PubMed Haag MD, Hofman A, Koudstaal PJ, Stricker BH, Breteler MM (2009) Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study. J Neurol Neurosurg Psychiatry 80(1):13–17PubMed
go back to reference Hamos JE, DeGennaro LJ, Drachman DA (1989) Synaptic loss in Alzheimer’s disease and other dementias. Neurology 39(3):355–361PubMed Hamos JE, DeGennaro LJ, Drachman DA (1989) Synaptic loss in Alzheimer’s disease and other dementias. Neurology 39(3):355–361PubMed
go back to reference Harris WS (1997a) n-3 fatty acids and serum lipoproteins: animal studies. Am J Clin Nutr 65(5 Suppl):1611S–1616SPubMed Harris WS (1997a) n-3 fatty acids and serum lipoproteins: animal studies. Am J Clin Nutr 65(5 Suppl):1611S–1616SPubMed
go back to reference Harris WS (1997b) n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 65(5 Suppl):1645S–1654SPubMed Harris WS (1997b) n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 65(5 Suppl):1645S–1654SPubMed
go back to reference Hartman RE, Wozniak DF, Nardi A, Olney JW, Sartorius L, Holtzman DM (2001) Behavioral phenotyping of GFAP-apoE3 and -apoE4 transgenic mice: apoE4 mice show profound working memory impairments in the absence of Alzheimer’s-like neuropathology. Exp Neurol 170(2):326–344. doi:10.1006/exnr.2001.7715 PubMed Hartman RE, Wozniak DF, Nardi A, Olney JW, Sartorius L, Holtzman DM (2001) Behavioral phenotyping of GFAP-apoE3 and -apoE4 transgenic mice: apoE4 mice show profound working memory impairments in the absence of Alzheimer’s-like neuropathology. Exp Neurol 170(2):326–344. doi:10.​1006/​exnr.​2001.​7715 PubMed
go back to reference Hirsch-Reinshagen V, Burgess BL, Wellington CL (2009) Why lipids are important for Alzheimer disease? Mol Cell Biochem 326(1–2):121–129PubMed Hirsch-Reinshagen V, Burgess BL, Wellington CL (2009) Why lipids are important for Alzheimer disease? Mol Cell Biochem 326(1–2):121–129PubMed
go back to reference Holscher C (1999) Stress impairs performance in spatial water maze learning tasks. Behav Brain Res 100(1–2):225–235PubMed Holscher C (1999) Stress impairs performance in spatial water maze learning tasks. Behav Brain Res 100(1–2):225–235PubMed
go back to reference Hooijmans CR, Van der Zee CE, Dederen PJ, Brouwer KM, Reijmer YD, van Groen T, Broersen LM, Lutjohann D, Heerschap A, Kiliaan AJ (2009) DHA and cholesterol containing diets influence Alzheimer-like pathology, cognition and cerebral vasculature in APPswe/PS1dE9 mice. Neurobiol Dis 33(3):482–498PubMed Hooijmans CR, Van der Zee CE, Dederen PJ, Brouwer KM, Reijmer YD, van Groen T, Broersen LM, Lutjohann D, Heerschap A, Kiliaan AJ (2009) DHA and cholesterol containing diets influence Alzheimer-like pathology, cognition and cerebral vasculature in APPswe/PS1dE9 mice. Neurobiol Dis 33(3):482–498PubMed
go back to reference Huang Y (2006) Apolipoprotein E and Alzheimer disease. Neurology 66 (2 Suppl 1):S79–S85 Huang Y (2006) Apolipoprotein E and Alzheimer disease. Neurology 66 (2 Suppl 1):S79–S85
go back to reference Irizarry MC, Soriano F, McNamara M, Page KJ, Schenk D, Games D, Hyman BT (1997) Abeta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse. J Neurosci 17(18):7053–7059PubMed Irizarry MC, Soriano F, McNamara M, Page KJ, Schenk D, Games D, Hyman BT (1997) Abeta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse. J Neurosci 17(18):7053–7059PubMed
go back to reference Isik T, Ayhan E, Uyarel H, Ergelen M, Tanboga IH, Kurt M, Korkmaz AF, Kaya A, Aksakal E, Sevimli S (2012) Increased mean platelet volume associated with extent of slow coronary flow. Cardiol J 19(4):355–362PubMed Isik T, Ayhan E, Uyarel H, Ergelen M, Tanboga IH, Kurt M, Korkmaz AF, Kaya A, Aksakal E, Sevimli S (2012) Increased mean platelet volume associated with extent of slow coronary flow. Cardiol J 19(4):355–362PubMed
go back to reference Ito T, Azuma J (2004) Taurine is a possible anti-atherosclerotic agent. Nihon Yakurigaku Zasshi 123(5):311–317PubMed Ito T, Azuma J (2004) Taurine is a possible anti-atherosclerotic agent. Nihon Yakurigaku Zasshi 123(5):311–317PubMed
go back to reference Jahn R, Sudhof TC (1993) Synaptic vesicle traffic: rush hour in the nerve terminal. J Neurochem 61(1):12–21PubMed Jahn R, Sudhof TC (1993) Synaptic vesicle traffic: rush hour in the nerve terminal. J Neurochem 61(1):12–21PubMed
go back to reference Jankowsky JL, Slunt HH, Ratovitski T, Jenkins NA, Copeland NG, Borchelt DR (2001) Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol Eng 17(6):157–165PubMed Jankowsky JL, Slunt HH, Ratovitski T, Jenkins NA, Copeland NG, Borchelt DR (2001) Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol Eng 17(6):157–165PubMed
go back to reference Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Wagner SL, Younkin SG, Borchelt DR (2004) Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13(3):159–170PubMed Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Wagner SL, Younkin SG, Borchelt DR (2004) Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13(3):159–170PubMed
go back to reference Jansen D, Janssen CI, Vanmierlo T, Dederen PJ, van Rooij D, Zinnhardt B, Nobelen CL, Janssen AL, Hafkemeijer A, Mutsaers MP, Doedee AM, Kuipers AA, Broersen LM, Mulder M, Kiliaan AJ (2012) Cholesterol and synaptic compensatory mechanisms in Alzheimer’s disease mice brain during aging. J Alzheimers Dis 31(4):813–826. doi:10.3233/JAD-2012-120298 PubMed Jansen D, Janssen CI, Vanmierlo T, Dederen PJ, van Rooij D, Zinnhardt B, Nobelen CL, Janssen AL, Hafkemeijer A, Mutsaers MP, Doedee AM, Kuipers AA, Broersen LM, Mulder M, Kiliaan AJ (2012) Cholesterol and synaptic compensatory mechanisms in Alzheimer’s disease mice brain during aging. J Alzheimers Dis 31(4):813–826. doi:10.​3233/​JAD-2012-120298 PubMed
go back to reference Jicha GA, Markesbery WR (2010) Omega-3 fatty acids: potential role in the management of early Alzheimer’s disease. Clin Interv Aging 5:45–61PubMedCentralPubMed Jicha GA, Markesbery WR (2010) Omega-3 fatty acids: potential role in the management of early Alzheimer’s disease. Clin Interv Aging 5:45–61PubMedCentralPubMed
go back to reference Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA (2000) Statins and the risk of dementia. Lancet 356(9242):1627–1631PubMed Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA (2000) Statins and the risk of dementia. Lancet 356(9242):1627–1631PubMed
go back to reference Jin K, Galvan V, Xie L, Mao XO, Gorostiza OF, Bredesen DE, Greenberg DA (2004a) Enhanced neurogenesis in Alzheimer’s disease transgenic (PDGF-APPSw, Ind) mice. Proc Natl Acad Sci USA 101(36):13363–13367PubMedCentralPubMed Jin K, Galvan V, Xie L, Mao XO, Gorostiza OF, Bredesen DE, Greenberg DA (2004a) Enhanced neurogenesis in Alzheimer’s disease transgenic (PDGF-APPSw, Ind) mice. Proc Natl Acad Sci USA 101(36):13363–13367PubMedCentralPubMed
go back to reference Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA (2004b) Increased hippocampal neurogenesis in Alzheimer’s disease. Proc Natl Acad Sci USA 101(1):343–347PubMedCentralPubMed Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA (2004b) Increased hippocampal neurogenesis in Alzheimer’s disease. Proc Natl Acad Sci USA 101(1):343–347PubMedCentralPubMed
go back to reference Joseph JA, Shukitt-Hale B, Denisova NA, Prior RL, Cao G, Martin A, Taglialatela G, Bickford PC (1998) Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits. J Neurosci 18(19):8047–8055PubMed Joseph JA, Shukitt-Hale B, Denisova NA, Prior RL, Cao G, Martin A, Taglialatela G, Bickford PC (1998) Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits. J Neurosci 18(19):8047–8055PubMed
go back to reference Kamphuis PJ, Scheltens P (2010) Can nutrients prevent or delay onset of Alzheimer’s disease? J Alzheimers Dis 20(3):765–775PubMed Kamphuis PJ, Scheltens P (2010) Can nutrients prevent or delay onset of Alzheimer’s disease? J Alzheimers Dis 20(3):765–775PubMed
go back to reference Kamphuis PJ, Verhey FR, Olde Rikkert MG, Twisk JW, Swinkels SH, Scheltens P (2011) Efficacy of a medical food on cognition in Alzheimer’s disease: results from secondary analyses of a randomized, controlled trial. J Nutr Health Aging 15(8):720–724PubMed Kamphuis PJ, Verhey FR, Olde Rikkert MG, Twisk JW, Swinkels SH, Scheltens P (2011) Efficacy of a medical food on cognition in Alzheimer’s disease: results from secondary analyses of a randomized, controlled trial. J Nutr Health Aging 15(8):720–724PubMed
go back to reference Kandiah N, Feldman HH (2009) Therapeutic potential of statins in Alzheimer’s disease. J Neurol Sci 283(1–2):230–234PubMed Kandiah N, Feldman HH (2009) Therapeutic potential of statins in Alzheimer’s disease. J Neurol Sci 283(1–2):230–234PubMed
go back to reference Kaneto H (1997) Learning/memory processes under stress conditions. Behav Brain Res 83(1–2):71–74PubMed Kaneto H (1997) Learning/memory processes under stress conditions. Behav Brain Res 83(1–2):71–74PubMed
go back to reference Kariv-Inbal Z, Yacobson S, Berkecz R, Peter M, Janaky T, Lutjohann D, Broersen LM, Hartmann T, Michaelson DM (2012) The isoform-specific pathological effects of apoE4 in vivo are prevented by a fish oil (DHA) diet and are modified by cholesterol. J Alzheimers Dis 28(3):667–683. doi:10.3233/JAD-2011-111265 PubMed Kariv-Inbal Z, Yacobson S, Berkecz R, Peter M, Janaky T, Lutjohann D, Broersen LM, Hartmann T, Michaelson DM (2012) The isoform-specific pathological effects of apoE4 in vivo are prevented by a fish oil (DHA) diet and are modified by cholesterol. J Alzheimers Dis 28(3):667–683. doi:10.​3233/​JAD-2011-111265 PubMed
go back to reference Kato H, Kogure K (1999) Biochemical and molecular characteristics of the brain with developing cerebral infarction. Cell Mol Neurobiol 19(1):93–108PubMed Kato H, Kogure K (1999) Biochemical and molecular characteristics of the brain with developing cerebral infarction. Cell Mol Neurobiol 19(1):93–108PubMed
go back to reference Kawakita E, Hashimoto M, Shido O (2006) Docosahexaenoic acid promotes neurogenesis in vitro and in vivo. Neuroscience 139(3):991–997PubMed Kawakita E, Hashimoto M, Shido O (2006) Docosahexaenoic acid promotes neurogenesis in vitro and in vivo. Neuroscience 139(3):991–997PubMed
go back to reference Kee NJ, Preston E, Wojtowicz JM (2001) Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat. Exp Brain Res Experimentelle Hirnforschung 136(3):313–320 Kee NJ, Preston E, Wojtowicz JM (2001) Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat. Exp Brain Res Experimentelle Hirnforschung 136(3):313–320
go back to reference Kennan RP, Zhong J, Gore JC (1994) Intravascular susceptibility contrast mechanisms in tissues. Magn Reson Med 31(1):9–21PubMed Kennan RP, Zhong J, Gore JC (1994) Intravascular susceptibility contrast mechanisms in tissues. Magn Reson Med 31(1):9–21PubMed
go back to reference King DL, Arendash GW (2002) Maintained synaptophysin immunoreactivity in Tg2576 transgenic mice during aging: correlations with cognitive impairment. Brain Res 926(1–2):58–68PubMed King DL, Arendash GW (2002) Maintained synaptophysin immunoreactivity in Tg2576 transgenic mice during aging: correlations with cognitive impairment. Brain Res 926(1–2):58–68PubMed
go back to reference Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A (2001) Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ Clin Res 322(7300):1447–1451 Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A (2001) Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ Clin Res 322(7300):1447–1451
go back to reference Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kareholt I, Winblad B, Helkala EL, Tuomilehto J, Soininen H, Nissinen A (2005) Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 62(10):1556–1560PubMed Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kareholt I, Winblad B, Helkala EL, Tuomilehto J, Soininen H, Nissinen A (2005) Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 62(10):1556–1560PubMed
go back to reference Knouff C, Hinsdale ME, Mezdour H, Altenburg MK, Watanabe M, Quarfordt SH, Sullivan PM, Maeda N (1999) ApoE structure determines VLDL clearance and atherosclerosis risk in mice. J Clin Invest 103(11):1579–1586PubMedCentralPubMed Knouff C, Hinsdale ME, Mezdour H, Altenburg MK, Watanabe M, Quarfordt SH, Sullivan PM, Maeda N (1999) ApoE structure determines VLDL clearance and atherosclerosis risk in mice. J Clin Invest 103(11):1579–1586PubMedCentralPubMed
go back to reference Kondo Y, Murakami S, Oda H, Nagate T (2000) Taurine reduces atherosclerotic lesion development in apolipoprotein E-deficient mice. Adv Exp Med Biol 483:193–202PubMed Kondo Y, Murakami S, Oda H, Nagate T (2000) Taurine reduces atherosclerotic lesion development in apolipoprotein E-deficient mice. Adv Exp Med Biol 483:193–202PubMed
go back to reference Kotani S, Sakaguchi E, Warashina S, Matsukawa N, Ishikura Y, Kiso Y, Sakakibara M, Yoshimoto T, Guo J, Yamashima T (2006) Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction. Neurosci Res 56(2):159–164PubMed Kotani S, Sakaguchi E, Warashina S, Matsukawa N, Ishikura Y, Kiso Y, Sakakibara M, Yoshimoto T, Guo J, Yamashima T (2006) Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction. Neurosci Res 56(2):159–164PubMed
go back to reference Krzywkowski P, Ghribi O, Gagne J, Chabot C, Kar S, Rochford J, Massicotte G, Poirier J (1999) Cholinergic systems and long-term potentiation in memory-impaired apolipoprotein E-deficient mice. Neuroscience 92(4):1273–1286PubMed Krzywkowski P, Ghribi O, Gagne J, Chabot C, Kar S, Rochford J, Massicotte G, Poirier J (1999) Cholinergic systems and long-term potentiation in memory-impaired apolipoprotein E-deficient mice. Neuroscience 92(4):1273–1286PubMed
go back to reference LaRosa JC, Hunninghake D, Bush D, Criqui MH, Getz GS, Gotto AM Jr, Grundy SM, Rakita L, Robertson RM, Weisfeldt ML et al (1990) The cholesterol facts. A summary of the evidence relating dietary fats, serum cholesterol, and coronary heart disease. A joint statement by the American Heart Association and the National Heart, Lung, and Blood Institute. The Task Force on Cholesterol Issues, American Heart Association. Circulation 81(5):1721–1733 LaRosa JC, Hunninghake D, Bush D, Criqui MH, Getz GS, Gotto AM Jr, Grundy SM, Rakita L, Robertson RM, Weisfeldt ML et al (1990) The cholesterol facts. A summary of the evidence relating dietary fats, serum cholesterol, and coronary heart disease. A joint statement by the American Heart Association and the National Heart, Lung, and Blood Institute. The Task Force on Cholesterol Issues, American Heart Association. Circulation 81(5):1721–1733
go back to reference Lavie CJ, Milani RV, Mehra MR, Ventura HO (2009) Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol 54(7):585–594PubMed Lavie CJ, Milani RV, Mehra MR, Ventura HO (2009) Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol 54(7):585–594PubMed
go back to reference Leaf A, Kang JX, Xiao YF, Billman GE (2003) Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Circulation 107(21):2646–2652PubMed Leaf A, Kang JX, Xiao YF, Billman GE (2003) Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Circulation 107(21):2646–2652PubMed
go back to reference Lekieffre D, Callebert J, Plotkine M, Boulu RG (1992) Concomitant increases in the extracellular concentrations of excitatory and inhibitory amino acids in the rat hippocampus during forebrain ischemia. Neurosci Lett 137(1):78–82PubMed Lekieffre D, Callebert J, Plotkine M, Boulu RG (1992) Concomitant increases in the extracellular concentrations of excitatory and inhibitory amino acids in the rat hippocampus during forebrain ischemia. Neurosci Lett 137(1):78–82PubMed
go back to reference Leuba G, Savioz A, Vernay A, Carnal B, Kraftsik R, Tardif E, Riederer I, Riederer BM (2008) Differential changes in synaptic proteins in the Alzheimer frontal cortex with marked increase in PSD-95 postsynaptic protein. J Alzheimers Dis 15(1):139–151PubMed Leuba G, Savioz A, Vernay A, Carnal B, Kraftsik R, Tardif E, Riederer I, Riederer BM (2008) Differential changes in synaptic proteins in the Alzheimer frontal cortex with marked increase in PSD-95 postsynaptic protein. J Alzheimers Dis 15(1):139–151PubMed
go back to reference Levi O, Michaelson DM (2007) Environmental enrichment stimulates neurogenesis in apolipoprotein E3 and neuronal apoptosis in apolipoprotein E4 transgenic mice. J Neurochem 100(1):202–210PubMed Levi O, Michaelson DM (2007) Environmental enrichment stimulates neurogenesis in apolipoprotein E3 and neuronal apoptosis in apolipoprotein E4 transgenic mice. J Neurochem 100(1):202–210PubMed
go back to reference Levi O, Jongen-Relo AL, Feldon J, Michaelson DM (2005) Brain area- and isoform-specific inhibition of synaptic plasticity by apoE4. J Neurol Sci 229–230:241–248PubMed Levi O, Jongen-Relo AL, Feldon J, Michaelson DM (2005) Brain area- and isoform-specific inhibition of synaptic plasticity by apoE4. J Neurol Sci 229–230:241–248PubMed
go back to reference Lutjohann D, Brzezinka A, Barth E, Abramowski D, Staufenbiel M, von Bergmann K, Beyreuther K, Multhaup G, Bayer TA (2002) Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain. J Lipid Res 43(7):1078–1085PubMed Lutjohann D, Brzezinka A, Barth E, Abramowski D, Staufenbiel M, von Bergmann K, Beyreuther K, Multhaup G, Bayer TA (2002) Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain. J Lipid Res 43(7):1078–1085PubMed
go back to reference Lutjohann D, Stroick M, Bertsch T, Kuhl S, Lindenthal B, Thelen K, Andersson U, Bjorkhem I, Bergmann Kv K, Fassbender K (2004) High doses of simvastatin, pravastatin, and cholesterol reduce brain cholesterol synthesis in guinea pigs. Steroids 69(6):431–438 Lutjohann D, Stroick M, Bertsch T, Kuhl S, Lindenthal B, Thelen K, Andersson U, Bjorkhem I, Bergmann Kv K, Fassbender K (2004) High doses of simvastatin, pravastatin, and cholesterol reduce brain cholesterol synthesis in guinea pigs. Steroids 69(6):431–438
go back to reference Lynch JR, Morgan D, Mance J, Matthew WD, Laskowitz DT (2001) Apolipoprotein E modulates glial activation and the endogenous central nervous system inflammatory response. J Neuroimmunol 114(1–2):107–113PubMed Lynch JR, Morgan D, Mance J, Matthew WD, Laskowitz DT (2001) Apolipoprotein E modulates glial activation and the endogenous central nervous system inflammatory response. J Neuroimmunol 114(1–2):107–113PubMed
go back to reference Mahley RW (1988) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240(4852):622–630 Mahley RW (1988) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240(4852):622–630
go back to reference Masliah E, Sisk A, Mallory M, Mucke L, Schenk D, Games D (1996) Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer’s disease. J Neurosci 16(18):5795–5811PubMed Masliah E, Sisk A, Mallory M, Mucke L, Schenk D, Games D (1996) Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer’s disease. J Neurosci 16(18):5795–5811PubMed
go back to reference Mauch DH, Nagler K, Schumacher S, Goritz C, Muller EC, Otto A, Pfrieger FW (2001) CNS synaptogenesis promoted by glia-derived cholesterol. Science 294(5545):1354–1357 Mauch DH, Nagler K, Schumacher S, Goritz C, Muller EC, Otto A, Pfrieger FW (2001) CNS synaptogenesis promoted by glia-derived cholesterol. Science 294(5545):1354–1357
go back to reference Mayeux R, Small SA, Tang M, Tycko B, Stern Y (2001) Memory performance in healthy elderly without Alzheimer’s disease: effects of time and apolipoprotein-E. Neurobiol Aging 22(4):683–689PubMed Mayeux R, Small SA, Tang M, Tycko B, Stern Y (2001) Memory performance in healthy elderly without Alzheimer’s disease: effects of time and apolipoprotein-E. Neurobiol Aging 22(4):683–689PubMed
go back to reference McGuinness B, Craig D, Bullock R, Passmore P (2009) Statins for the prevention of dementia. Cochrane Database System Rev (Online) (2):CD003160 McGuinness B, Craig D, Bullock R, Passmore P (2009) Statins for the prevention of dementia. Cochrane Database System Rev (Online) (2):CD003160
go back to reference Methia N, Andre P, Hafezi-Moghadam A, Economopoulos M, Thomas KL, Wagner DD (2001) ApoE deficiency compromises the blood brain barrier especially after injury. Mol Med 7(12):810–815PubMedCentralPubMed Methia N, Andre P, Hafezi-Moghadam A, Economopoulos M, Thomas KL, Wagner DD (2001) ApoE deficiency compromises the blood brain barrier especially after injury. Mol Med 7(12):810–815PubMedCentralPubMed
go back to reference Miyata M, Smith JD (1996) Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat Genet 14(1):55–61PubMed Miyata M, Smith JD (1996) Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat Genet 14(1):55–61PubMed
go back to reference Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L (2000) High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 20(11):4050–4058PubMed Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L (2000) High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 20(11):4050–4058PubMed
go back to reference Mulder M, Koopmans G, Wassink G, Al Mansouri G, Simard ML, Havekes LM, Prickaerts J, Blokland A (2007) LDL receptor deficiency results in decreased cell proliferation and presynaptic bouton density in the murine hippocampus. Neurosci Res 59(3):251–256PubMed Mulder M, Koopmans G, Wassink G, Al Mansouri G, Simard ML, Havekes LM, Prickaerts J, Blokland A (2007) LDL receptor deficiency results in decreased cell proliferation and presynaptic bouton density in the murine hippocampus. Neurosci Res 59(3):251–256PubMed
go back to reference Nagy Z, Esiri MM, Jobst KA, Johnston C, Litchfield S, Sim E, Smith AD (1995) Influence of the apolipoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer’s disease. Neuroscience 69(3):757–761PubMed Nagy Z, Esiri MM, Jobst KA, Johnston C, Litchfield S, Sim E, Smith AD (1995) Influence of the apolipoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer’s disease. Neuroscience 69(3):757–761PubMed
go back to reference Nakashima Y, Plump AS, Raines EW, Breslow JL, Ross R (1994) ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb 14(1):133–140PubMed Nakashima Y, Plump AS, Raines EW, Breslow JL, Ross R (1994) ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb 14(1):133–140PubMed
go back to reference Naliwaiko K, Araujo RL, da Fonseca RV, Castilho JC, Andreatini R, Bellissimo MI, Oliveira BH, Martins EF, Curi R, Fernandes LC, Ferraz AC (2004) Effects of fish oil on the central nervous system: a new potential antidepressant? Nutr Neurosci 7(2):91–99PubMed Naliwaiko K, Araujo RL, da Fonseca RV, Castilho JC, Andreatini R, Bellissimo MI, Oliveira BH, Martins EF, Curi R, Fernandes LC, Ferraz AC (2004) Effects of fish oil on the central nervous system: a new potential antidepressant? Nutr Neurosci 7(2):91–99PubMed
go back to reference Ohm TG, Scharnagl H, Marz W, Bohl J (1999) Apolipoprotein E isoforms and the development of low and high Braak stages of Alzheimer’s disease-related lesions. Acta Neuropathol 98(3):273–280PubMed Ohm TG, Scharnagl H, Marz W, Bohl J (1999) Apolipoprotein E isoforms and the development of low and high Braak stages of Alzheimer’s disease-related lesions. Acta Neuropathol 98(3):273–280PubMed
go back to reference Oitzl MS, Mulder M, Lucassen PJ, Havekes LM, Grootendorst J, de Kloet ER (1997) Severe learning deficits in apolipoprotein E-knockout mice in a water maze task. Brain Res 752(1–2):189–196PubMed Oitzl MS, Mulder M, Lucassen PJ, Havekes LM, Grootendorst J, de Kloet ER (1997) Severe learning deficits in apolipoprotein E-knockout mice in a water maze task. Brain Res 752(1–2):189–196PubMed
go back to reference Oja SS, Saransaari P (1996) Taurine as osmoregulator and neuromodulator in the brain. Metab Brain Dis 11(2):153–164PubMed Oja SS, Saransaari P (1996) Taurine as osmoregulator and neuromodulator in the brain. Metab Brain Dis 11(2):153–164PubMed
go back to reference Oksman M, Iivonen H, Hogyes E, Amtul Z, Penke B, Leenders I, Broersen L, Lutjohann D, Hartmann T, Tanila H (2006) Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic mice. Neurobiol Dis 23(3):563–572PubMed Oksman M, Iivonen H, Hogyes E, Amtul Z, Penke B, Leenders I, Broersen L, Lutjohann D, Hartmann T, Tanila H (2006) Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic mice. Neurobiol Dis 23(3):563–572PubMed
go back to reference Okuda N, Ueshima H, Okayama A, Saitoh S, Nakagawa H, Rodriguez BL, Sakata K, Choudhury SR, Curb JD, Stamler J (2005) Relation of long chain n-3 polyunsaturated fatty acid intake to serum high density lipoprotein cholesterol among Japanese men in Japan and Japanese-American men in Hawaii: the INTERLIPID study. Atherosclerosis 178(2):371–379PubMed Okuda N, Ueshima H, Okayama A, Saitoh S, Nakagawa H, Rodriguez BL, Sakata K, Choudhury SR, Curb JD, Stamler J (2005) Relation of long chain n-3 polyunsaturated fatty acid intake to serum high density lipoprotein cholesterol among Japanese men in Japan and Japanese-American men in Hawaii: the INTERLIPID study. Atherosclerosis 178(2):371–379PubMed
go back to reference Patterson MB, Schnell AH, Martin RJ, Mendez MF, Smyth KA, Whitehouse PJ (1990) Assessment of behavioral and affective symptoms in Alzheimer’s disease. J Geriatr Psychiatry Neurol 3(1):21–30PubMed Patterson MB, Schnell AH, Martin RJ, Mendez MF, Smyth KA, Whitehouse PJ (1990) Assessment of behavioral and affective symptoms in Alzheimer’s disease. J Geriatr Psychiatry Neurol 3(1):21–30PubMed
go back to reference Pfrieger FW (2003) Cholesterol homeostasis and function in neurons of the central nervous system. Cell Mol Life Sci 60(6):1158–1171PubMed Pfrieger FW (2003) Cholesterol homeostasis and function in neurons of the central nervous system. Cell Mol Life Sci 60(6):1158–1171PubMed
go back to reference Piedrahita JA, Zhang SH, Hagaman JR, Oliver PM, Maeda N (1992) Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc Natl Acad Sci USA 89(10):4471–4475PubMedCentralPubMed Piedrahita JA, Zhang SH, Hagaman JR, Oliver PM, Maeda N (1992) Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc Natl Acad Sci USA 89(10):4471–4475PubMedCentralPubMed
go back to reference Plump AS, Smith JD, Hayek T, Aalto-Setala K, Walsh A, Verstuyft JG, Rubin EM, Breslow JL (1992) Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 71(2):343–353PubMed Plump AS, Smith JD, Hayek T, Aalto-Setala K, Walsh A, Verstuyft JG, Rubin EM, Breslow JL (1992) Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 71(2):343–353PubMed
go back to reference Poirier J, Minnich A, Davignon J (1995) Apolipoprotein E, synaptic plasticity and Alzheimer’s disease. Ann Med 27(6):663–670PubMed Poirier J, Minnich A, Davignon J (1995) Apolipoprotein E, synaptic plasticity and Alzheimer’s disease. Ann Med 27(6):663–670PubMed
go back to reference Premkumar DR, Cohen DL, Hedera P, Friedland RP, Kalaria RN (1996) Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer’s disease. Am J Pathol 148(6):2083–2095PubMedCentralPubMed Premkumar DR, Cohen DL, Hedera P, Friedland RP, Kalaria RN (1996) Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer’s disease. Am J Pathol 148(6):2083–2095PubMedCentralPubMed
go back to reference Pugh PL, Richardson JC, Bate ST, Upton N, Sunter D (2007) Non-cognitive behaviours in an APP/PS1 transgenic model of Alzheimer’s disease. Behav Brain Res 178(1):18–28PubMed Pugh PL, Richardson JC, Bate ST, Upton N, Sunter D (2007) Non-cognitive behaviours in an APP/PS1 transgenic model of Alzheimer’s disease. Behav Brain Res 178(1):18–28PubMed
go back to reference Raber J, Wong D, Buttini M, Orth M, Bellosta S, Pitas RE, Mahley RW, Mucke L (1998) Isoform-specific effects of human apolipoprotein E on brain function revealed in ApoE knockout mice: increased susceptibility of females. Proc Natl Acad Sci USA 95(18):10914–10919PubMedCentralPubMed Raber J, Wong D, Buttini M, Orth M, Bellosta S, Pitas RE, Mahley RW, Mucke L (1998) Isoform-specific effects of human apolipoprotein E on brain function revealed in ApoE knockout mice: increased susceptibility of females. Proc Natl Acad Sci USA 95(18):10914–10919PubMedCentralPubMed
go back to reference Raber J, Akana SF, Bhatnagar S, Dallman MF, Wong D, Mucke L (2000) Hypothalamic-pituitary-adrenal dysfunction in Apoe(−/−) mice: possible role in behavioral and metabolic alterations. J Neurosci 20(5):2064–2071PubMed Raber J, Akana SF, Bhatnagar S, Dallman MF, Wong D, Mucke L (2000) Hypothalamic-pituitary-adrenal dysfunction in Apoe(−/−) mice: possible role in behavioral and metabolic alterations. J Neurosci 20(5):2064–2071PubMed
go back to reference Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123(11):1939–1951PubMed Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123(11):1939–1951PubMed
go back to reference Revett TJ, Baker GB, Jhamandas J, Kar S (2013) Glutamate system, amyloid ss peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology. J Psychiatry Neurosci 38(1):6–23. doi:10.1503/jpn.110190 PubMedCentralPubMed Revett TJ, Baker GB, Jhamandas J, Kar S (2013) Glutamate system, amyloid ss peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology. J Psychiatry Neurosci 38(1):6–23. doi:10.​1503/​jpn.​110190 PubMedCentralPubMed
go back to reference Rijpma A, Jansen D, Arnoldussen IAC, Fang XT, Wiesmann M, Mutsaers MPC, Dederen PJ, Janssen CIF, Kiliaan AJ (2013) Sex Differences in Presynaptic Density and Neurogenesis in Middle-Aged ApoE4 and ApoE Knockout Mice. J Neurodegener Dis 2013:9. doi:10.1155/2013/531326 Rijpma A, Jansen D, Arnoldussen IAC, Fang XT, Wiesmann M, Mutsaers MPC, Dederen PJ, Janssen CIF, Kiliaan AJ (2013) Sex Differences in Presynaptic Density and Neurogenesis in Middle-Aged ApoE4 and ApoE Knockout Mice. J Neurodegener Dis 2013:9. doi:10.​1155/​2013/​531326
go back to reference Rogers PJ, Appleton KM, Kessler D, Peters TJ, Gunnell D, Hayward RC, Heatherley SV, Christian LM, McNaughton SA, Ness AR (2008) No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial. Br J Nutr 99(2):421–431. doi:10.1017/S0007114507801097 PubMed Rogers PJ, Appleton KM, Kessler D, Peters TJ, Gunnell D, Hayward RC, Heatherley SV, Christian LM, McNaughton SA, Ness AR (2008) No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial. Br J Nutr 99(2):421–431. doi:10.​1017/​S000711450780109​7 PubMed
go back to reference Rutten BP, Wirths O, Van de Berg WD, Lichtenthaler SF, Vehoff J, Steinbusch HW, Korr H, Beyreuther K, Multhaup G, Bayer TA, Schmitz C (2003) No alterations of hippocampal neuronal number and synaptic bouton number in a transgenic mouse model expressing the beta-cleaved C-terminal APP fragment. Neurobiol Dis 12(2):110–120PubMed Rutten BP, Wirths O, Van de Berg WD, Lichtenthaler SF, Vehoff J, Steinbusch HW, Korr H, Beyreuther K, Multhaup G, Bayer TA, Schmitz C (2003) No alterations of hippocampal neuronal number and synaptic bouton number in a transgenic mouse model expressing the beta-cleaved C-terminal APP fragment. Neurobiol Dis 12(2):110–120PubMed
go back to reference Rutten BP, Van der Kolk NM, Schafer S, van Zandvoort MA, Bayer TA, Steinbusch HW, Schmitz C (2005) Age-related loss of synaptophysin immunoreactive presynaptic boutons within the hippocampus of APP751SL, PS1M146L, and APP751SL/PS1M146L transgenic mice. Am J Pathol 167(1):161–173PubMedCentralPubMed Rutten BP, Van der Kolk NM, Schafer S, van Zandvoort MA, Bayer TA, Steinbusch HW, Schmitz C (2005) Age-related loss of synaptophysin immunoreactive presynaptic boutons within the hippocampus of APP751SL, PS1M146L, and APP751SL/PS1M146L transgenic mice. Am J Pathol 167(1):161–173PubMedCentralPubMed
go back to reference Sacks FM, Katan M (2002) Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease. Am J Med 113(Suppl 9B):13S–24S Sacks FM, Katan M (2002) Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease. Am J Med 113(Suppl 9B):13S–24S
go back to reference Saransaari P, Oja SS (1997) Enhanced taurine release in cell-damaging conditions in the developing and ageing mouse hippocampus. Neuroscience 79(3):847–854PubMed Saransaari P, Oja SS (1997) Enhanced taurine release in cell-damaging conditions in the developing and ageing mouse hippocampus. Neuroscience 79(3):847–854PubMed
go back to reference Savelkoul PJ, Janickova H, Kuipers AA, Hageman RJ, Kamphuis PJ, Dolezal V, Broersen LM (2012) A specific multi-nutrient formulation enhances M1 muscarinic acetylcholine receptor responses in vitro. J Neurochem 120(4):631–640PubMed Savelkoul PJ, Janickova H, Kuipers AA, Hageman RJ, Kamphuis PJ, Dolezal V, Broersen LM (2012) A specific multi-nutrient formulation enhances M1 muscarinic acetylcholine receptor responses in vitro. J Neurochem 120(4):631–640PubMed
go back to reference Sawiak SJ, Wood NI, Williams GB, Morton AJ, Carpenter TA (2009) Voxel-based morphometry in the R6/2 transgenic mouse reveals differences between genotypes not seen with manual 2D morphometry. Neurobiol Dis 33(1):20–27PubMed Sawiak SJ, Wood NI, Williams GB, Morton AJ, Carpenter TA (2009) Voxel-based morphometry in the R6/2 transgenic mouse reveals differences between genotypes not seen with manual 2D morphometry. Neurobiol Dis 33(1):20–27PubMed
go back to reference Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins SJ, Au R, Tucker KL, Kyle DJ, Wilson PW, Wolf PA (2006) Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol 63(11):1545–1550PubMed Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins SJ, Au R, Tucker KL, Kyle DJ, Wilson PW, Wolf PA (2006) Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol 63(11):1545–1550PubMed
go back to reference Scheff SW, Price DA (1998) Synaptic density in the inner molecular layer of the hippocampal dentate gyrus in Alzheimer disease. J Neuropathol Exp Neurol 57(12):1146–1153PubMed Scheff SW, Price DA (1998) Synaptic density in the inner molecular layer of the hippocampal dentate gyrus in Alzheimer disease. J Neuropathol Exp Neurol 57(12):1146–1153PubMed
go back to reference Scheff SW, Price DA (2003) Synaptic pathology in Alzheimer’s disease: a review of ultrastructural studies. Neurobiol Aging 24(8):1029–1046PubMed Scheff SW, Price DA (2003) Synaptic pathology in Alzheimer’s disease: a review of ultrastructural studies. Neurobiol Aging 24(8):1029–1046PubMed
go back to reference Scheff SW, Sparks DL, Price DA (1996) Quantitative assessment of synaptic density in the outer molecular layer of the hippocampal dentate gyrus in Alzheimer’s disease. Dementia (Basel, Switzerland) 7(4):226–232 Scheff SW, Sparks DL, Price DA (1996) Quantitative assessment of synaptic density in the outer molecular layer of the hippocampal dentate gyrus in Alzheimer’s disease. Dementia (Basel, Switzerland) 7(4):226–232
go back to reference Scheff SW, Price DA, Schmitt FA, Mufson EJ (2006) Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 27(10):1372–1384PubMed Scheff SW, Price DA, Schmitt FA, Mufson EJ (2006) Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 27(10):1372–1384PubMed
go back to reference Scheltens P, Kamphuis PJ, Verhey FR, Olde Rikkert MG, Wurtman RJ, Wilkinson D, Twisk JW, Kurz A (2010) Efficacy of a medical food in mild Alzheimer’s disease: A randomized, controlled trial. Alzheimers Dement 6(1):1–10 e11. doi:10.1016/j.jalz.2009.10.003 Scheltens P, Kamphuis PJ, Verhey FR, Olde Rikkert MG, Wurtman RJ, Wilkinson D, Twisk JW, Kurz A (2010) Efficacy of a medical food in mild Alzheimer’s disease: A randomized, controlled trial. Alzheimers Dement 6(1):1–10 e11. doi:10.​1016/​j.​jalz.​2009.​10.​003
go back to reference Scheltens P, Twisk JW, Blesa R, Scarpini E, von Arnim CA, Bongers A, Harrison J, Swinkels SH, Stam CJ, de Waal H, Wurtman RJ, Wieggers RL, Vellas B, Kamphuis PJ (2012) Efficacy of Souvenaid in mild Alzheimer’s disease: results from a randomized, controlled trial. J Alzheimers Dis 31(1):225–236. doi:10.3233/JAD-2012-121189 PubMed Scheltens P, Twisk JW, Blesa R, Scarpini E, von Arnim CA, Bongers A, Harrison J, Swinkels SH, Stam CJ, de Waal H, Wurtman RJ, Wieggers RL, Vellas B, Kamphuis PJ (2012) Efficacy of Souvenaid in mild Alzheimer’s disease: results from a randomized, controlled trial. J Alzheimers Dis 31(1):225–236. doi:10.​3233/​JAD-2012-121189 PubMed
go back to reference Schipper HM (2011) Apolipoprotein E: implications for AD neurobiology, epidemiology and risk assessment. Neurobiol Aging 32(5):778–790PubMed Schipper HM (2011) Apolipoprotein E: implications for AD neurobiology, epidemiology and risk assessment. Neurobiol Aging 32(5):778–790PubMed
go back to reference Schipper P, Kiliaan AJ, Homberg JR (2011) A mixed polyunsaturated fatty acid diet normalizes hippocampal neurogenesis and reduces anxiety in serotonin transporter knockout rats. Behav Pharmacol 22(4):324–334PubMed Schipper P, Kiliaan AJ, Homberg JR (2011) A mixed polyunsaturated fatty acid diet normalizes hippocampal neurogenesis and reduces anxiety in serotonin transporter knockout rats. Behav Pharmacol 22(4):324–334PubMed
go back to reference Schmechel DE, Saunders AM, Strittmatter WJ, Crain BJ, Hulette CM, Joo SH, Pericak-Vance MA, Goldgaber D, Roses AD (1993) Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci USA 90(20):9649–9653PubMedCentralPubMed Schmechel DE, Saunders AM, Strittmatter WJ, Crain BJ, Hulette CM, Joo SH, Pericak-Vance MA, Goldgaber D, Roses AD (1993) Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci USA 90(20):9649–9653PubMedCentralPubMed
go back to reference Selkoe DJ (2002) Alzheimer’s disease is a synaptic failure. Science 298(5594):789–791 Selkoe DJ (2002) Alzheimer’s disease is a synaptic failure. Science 298(5594):789–791
go back to reference Shrivastava R, Vincent B, Gobron S, Cucuat N, John GW (2005) Evidence for growth-promoting effects of omega n-3 fatty acids alone and in combination with a specific vitamin and mineral complex in rat neuroblastoma cells. Nutr Neurosci 8(5–6):317–321PubMed Shrivastava R, Vincent B, Gobron S, Cucuat N, John GW (2005) Evidence for growth-promoting effects of omega n-3 fatty acids alone and in combination with a specific vitamin and mineral complex in rat neuroblastoma cells. Nutr Neurosci 8(5–6):317–321PubMed
go back to reference Shukla C, Bridges LR (1999) Regional distribution of tau, beta-amyloid and beta-amyloid precursor protein in the Alzheimer’s brain: a quantitative immunolabelling study. NeuroReport 10(18):3785–3789PubMed Shukla C, Bridges LR (1999) Regional distribution of tau, beta-amyloid and beta-amyloid precursor protein in the Alzheimer’s brain: a quantitative immunolabelling study. NeuroReport 10(18):3785–3789PubMed
go back to reference Simon P, Dupuis R, Costentin J (1994) Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions. Behav Brain Res 61(1):59–64PubMed Simon P, Dupuis R, Costentin J (1994) Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions. Behav Brain Res 61(1):59–64PubMed
go back to reference Skoog I, Gustafson D (2006) Update on hypertension and Alzheimer’s disease. Neurol Res 28(6):605–611PubMed Skoog I, Gustafson D (2006) Update on hypertension and Alzheimer’s disease. Neurol Res 28(6):605–611PubMed
go back to reference Socci DJ, Crandall BM, Arendash GW (1995) Chronic antioxidant treatment improves the cognitive performance of aged rats. Brain Res 693(1–2):88–94PubMed Socci DJ, Crandall BM, Arendash GW (1995) Chronic antioxidant treatment improves the cognitive performance of aged rats. Brain Res 693(1–2):88–94PubMed
go back to reference Sparks DL, Sabbagh MN, Connor DJ, Lopez J, Launer LJ, Browne P, Wasser D, Johnson-Traver S, Lochhead J, Ziolwolski C (2005) Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results. Arch Neurol 62(5):753–757PubMed Sparks DL, Sabbagh MN, Connor DJ, Lopez J, Launer LJ, Browne P, Wasser D, Johnson-Traver S, Lochhead J, Ziolwolski C (2005) Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results. Arch Neurol 62(5):753–757PubMed
go back to reference Specht CG, Schoepfer R (2001) Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6 J inbred mice. BMC Neurosci 2:11PubMedCentralPubMed Specht CG, Schoepfer R (2001) Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6 J inbred mice. BMC Neurosci 2:11PubMedCentralPubMed
go back to reference Streijger F, Oerlemans F, Ellenbroek BA, Jost CR, Wieringa B, Van der Zee CE (2005) Structural and behavioural consequences of double deficiency for creatine kinases BCK and UbCKmit. Behav Brain Res 157(2):219–234PubMed Streijger F, Oerlemans F, Ellenbroek BA, Jost CR, Wieringa B, Van der Zee CE (2005) Structural and behavioural consequences of double deficiency for creatine kinases BCK and UbCKmit. Behav Brain Res 157(2):219–234PubMed
go back to reference Takeuchi T, Iwanaga M, Harada E (2003) Possible regulatory mechanism of DHA-induced anti-stress reaction in rats. Brain Res 964(1):136–143PubMed Takeuchi T, Iwanaga M, Harada E (2003) Possible regulatory mechanism of DHA-induced anti-stress reaction in rats. Brain Res 964(1):136–143PubMed
go back to reference Tanabe Y, Hashimoto M, Sugioka K, Maruyama M, Fujii Y, Hagiwara R, Hara T, Hossain SM, Shido O (2004) Improvement of spatial cognition with dietary docosahexaenoic acid is associated with an increase in Fos expression in rat CA1 hippocampus. Clin Exp Pharmacol Physiol 31(10):700–703PubMed Tanabe Y, Hashimoto M, Sugioka K, Maruyama M, Fujii Y, Hagiwara R, Hara T, Hossain SM, Shido O (2004) Improvement of spatial cognition with dietary docosahexaenoic acid is associated with an increase in Fos expression in rat CA1 hippocampus. Clin Exp Pharmacol Physiol 31(10):700–703PubMed
go back to reference Taniuchi N, Niidome T, Goto Y, Akaike A, Kihara T, Sugimoto H (2007) Decreased proliferation of hippocampal progenitor cells in APPswe/PS1dE9 transgenic mice. NeuroReport 18(17):1801–1805PubMed Taniuchi N, Niidome T, Goto Y, Akaike A, Kihara T, Sugimoto H (2007) Decreased proliferation of hippocampal progenitor cells in APPswe/PS1dE9 transgenic mice. NeuroReport 18(17):1801–1805PubMed
go back to reference Teather LA, Wurtman RJ (2003) Dietary cytidine (5′)-diphosphocholine supplementation protects against development of memory deficits in aging rats. Prog Neuropsychopharmacol Biol Psychiatry 27(4):711–717PubMed Teather LA, Wurtman RJ (2003) Dietary cytidine (5′)-diphosphocholine supplementation protects against development of memory deficits in aging rats. Prog Neuropsychopharmacol Biol Psychiatry 27(4):711–717PubMed
go back to reference Teri L, Ferretti LE, Gibbons LE, Logsdon RG, McCurry SM, Kukull WA, McCormick WC, Bowen JD, Larson EB (1999) Anxiety of Alzheimer’s disease: prevalence, and comorbidity. J Gerontol 54(7):M348–M352 Teri L, Ferretti LE, Gibbons LE, Logsdon RG, McCurry SM, Kukull WA, McCormick WC, Bowen JD, Larson EB (1999) Anxiety of Alzheimer’s disease: prevalence, and comorbidity. J Gerontol 54(7):M348–M352
go back to reference Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30(4):572–580PubMed Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30(4):572–580PubMed
go back to reference Thelen KM, Rentsch KM, Gutteck U, Heverin M, Olin M, Andersson U, von Eckardstein A, Bjorkhem I, Lutjohann D (2006) Brain cholesterol synthesis in mice is affected by high dose of simvastatin but not of pravastatin. J Pharmacol Exp Therapeut 316(3):1146–1152 Thelen KM, Rentsch KM, Gutteck U, Heverin M, Olin M, Andersson U, von Eckardstein A, Bjorkhem I, Lutjohann D (2006) Brain cholesterol synthesis in mice is affected by high dose of simvastatin but not of pravastatin. J Pharmacol Exp Therapeut 316(3):1146–1152
go back to reference Tous M, Ferre N, Vilella E, Riu F, Camps J, Joven J (2004) Circulating blood cells modulate the atherosclerotic process in apolipoprotein E-deficient mice. Metab Clin Exp 53(1):95–100 Tous M, Ferre N, Vilella E, Riu F, Camps J, Joven J (2004) Circulating blood cells modulate the atherosclerotic process in apolipoprotein E-deficient mice. Metab Clin Exp 53(1):95–100
go back to reference Troen AM, Shea-Budgell M, Shukitt-Hale B, Smith DE, Selhub J, Rosenberg IH (2008) B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice. Proc Natl Acad Sci USA 105(34):12474–12479PubMedCentralPubMed Troen AM, Shea-Budgell M, Shukitt-Hale B, Smith DE, Selhub J, Rosenberg IH (2008) B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice. Proc Natl Acad Sci USA 105(34):12474–12479PubMedCentralPubMed
go back to reference Tsukada H, Kakiuchi T, Fukumoto D, Nishiyama S, Koga K (2000) Docosahexaenoic acid (DHA) improves the age-related impairment of the coupling mechanism between neuronal activation and functional cerebral blood flow response: a PET study in conscious monkeys. Brain Res 862(1–2):180–186PubMed Tsukada H, Kakiuchi T, Fukumoto D, Nishiyama S, Koga K (2000) Docosahexaenoic acid (DHA) improves the age-related impairment of the coupling mechanism between neuronal activation and functional cerebral blood flow response: a PET study in conscious monkeys. Brain Res 862(1–2):180–186PubMed
go back to reference Valente T, Hidalgo J, Bolea I, Ramirez B, Angles N, Reguant J, Morello JR, Gutierrez C, Boada M, Unzeta M (2009) A diet enriched in polyphenols and polyunsaturated fatty acids, LMN diet, induces neurogenesis in the subventricular zone and hippocampus of adult mouse brain. J Alzheimers Dis 18(4):849–865. doi:10.3233/JAD-2009-1188 PubMed Valente T, Hidalgo J, Bolea I, Ramirez B, Angles N, Reguant J, Morello JR, Gutierrez C, Boada M, Unzeta M (2009) A diet enriched in polyphenols and polyunsaturated fatty acids, LMN diet, induces neurogenesis in the subventricular zone and hippocampus of adult mouse brain. J Alzheimers Dis 18(4):849–865. doi:10.​3233/​JAD-2009-1188 PubMed
go back to reference van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Dullemeijer C, Olderikkert MG, Beekman AT, de Groot CP (2008) Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial. Neurology 71(6):430–438. doi:10.1212/01.wnl.0000324268.45138.86 PubMed van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Dullemeijer C, Olderikkert MG, Beekman AT, de Groot CP (2008) Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial. Neurology 71(6):430–438. doi:10.​1212/​01.​wnl.​0000324268.​45138.​86 PubMed
go back to reference Veinbergs I, Mallory M, Mante M, Rockenstein E, Gilbert JR, Masliah E (1999) Differential neurotrophic effects of apolipoprotein E in aged transgenic mice. Neurosci Lett 265(3):218–222PubMed Veinbergs I, Mallory M, Mante M, Rockenstein E, Gilbert JR, Masliah E (1999) Differential neurotrophic effects of apolipoprotein E in aged transgenic mice. Neurosci Lett 265(3):218–222PubMed
go back to reference Wang D, Zhao Y, Zhang Y, Zhang T, Shang X, Wang J, Liu Y, Kong Q, Sun B, Lili M, Liu X, Wang G, Li H (2013) Hypothermia protects against oxygen-glucose deprivation-induced neuronal injury by down-regulating the reverse transport of glutamate by astrocytes as mediated by neurons. Neuroscience. doi:10.1016/j.neuroscience.2013.01.056 Wang D, Zhao Y, Zhang Y, Zhang T, Shang X, Wang J, Liu Y, Kong Q, Sun B, Lili M, Liu X, Wang G, Li H (2013) Hypothermia protects against oxygen-glucose deprivation-induced neuronal injury by down-regulating the reverse transport of glutamate by astrocytes as mediated by neurons. Neuroscience. doi:10.​1016/​j.​neuroscience.​2013.​01.​056
go back to reference Weisgraber KH (1994) Apolipoprotein E: structure-function relationships. Adv Protein Chem 45:249–302PubMed Weisgraber KH (1994) Apolipoprotein E: structure-function relationships. Adv Protein Chem 45:249–302PubMed
go back to reference Whalley LJ, Deary IJ, Starr JM, Wahle KW, Rance KA, Bourne VJ, Fox HC (2008) n-3 Fatty acid erythrocyte membrane content, APOE varepsilon4, and cognitive variation: an observational follow-up study in late adulthood. Am J Clin Nutr 87(2):449–454PubMed Whalley LJ, Deary IJ, Starr JM, Wahle KW, Rance KA, Bourne VJ, Fox HC (2008) n-3 Fatty acid erythrocyte membrane content, APOE varepsilon4, and cognitive variation: an observational follow-up study in late adulthood. Am J Clin Nutr 87(2):449–454PubMed
go back to reference Yagita Y, Kitagawa K, Ohtsuki T, Takasawa K, Miyata T, Okano H, Hori M, Matsumoto M (2001) Neurogenesis by progenitor cells in the ischemic adult rat hippocampus. Stroke J Cereb Circul 32(8):1890–1896 Yagita Y, Kitagawa K, Ohtsuki T, Takasawa K, Miyata T, Okano H, Hori M, Matsumoto M (2001) Neurogenesis by progenitor cells in the ischemic adult rat hippocampus. Stroke J Cereb Circul 32(8):1890–1896
go back to reference Yamada K, Tanaka T, Han D, Senzaki K, Kameyama T, Nabeshima T (1999) Protective effects of idebenone and alpha-tocopherol on beta-amyloid-(1-42)-induced learning and memory deficits in rats: implication of oxidative stress in beta-amyloid-induced neurotoxicity in vivo. Eur J Neurosci 11(1):83–90PubMed Yamada K, Tanaka T, Han D, Senzaki K, Kameyama T, Nabeshima T (1999) Protective effects of idebenone and alpha-tocopherol on beta-amyloid-(1-42)-induced learning and memory deficits in rats: implication of oxidative stress in beta-amyloid-induced neurotoxicity in vivo. Eur J Neurosci 11(1):83–90PubMed
go back to reference Yao PJ, Bushlin I, Furukawa K (2005) Preserved synaptic vesicle recycling in hippocampal neurons in a mouse Alzheimer’s disease model. Biochem Biophys Res Commun 330(1):34–38PubMed Yao PJ, Bushlin I, Furukawa K (2005) Preserved synaptic vesicle recycling in hippocampal neurons in a mouse Alzheimer’s disease model. Biochem Biophys Res Commun 330(1):34–38PubMed
go back to reference Yavich L, Tanila H, Vepsäläinen S, Jäkälä P (2004) Role of alpha-synuclein in presynaptic dopamine recruitment. J Neurosci 24(49):11165–11170PubMed Yavich L, Tanila H, Vepsäläinen S, Jäkälä P (2004) Role of alpha-synuclein in presynaptic dopamine recruitment. J Neurosci 24(49):11165–11170PubMed
go back to reference Yavich L, Jäkälä P, Tanila H (2006) Abnormal compartmentalization of norepinephrine in mouse dentate gyrus in alpha-synuclein knockout and A30P transgenic mice. J Neurochem 99(3):724–732PubMed Yavich L, Jäkälä P, Tanila H (2006) Abnormal compartmentalization of norepinephrine in mouse dentate gyrus in alpha-synuclein knockout and A30P transgenic mice. J Neurochem 99(3):724–732PubMed
go back to reference Yu Y, He J, Zhang Y, Luo H, Zhu S, Yang Y, Zhao T, Wu J, Huang Y, Kong J, Tan Q, Li XM (2009) Increased hippocampal neurogenesis in the progressive stage of Alzheimer’s disease phenotype in an APP/PS1 double transgenic mouse model. Hippocampus 19(12):1247–1253PubMed Yu Y, He J, Zhang Y, Luo H, Zhu S, Yang Y, Zhao T, Wu J, Huang Y, Kong J, Tan Q, Li XM (2009) Increased hippocampal neurogenesis in the progressive stage of Alzheimer’s disease phenotype in an APP/PS1 double transgenic mouse model. Hippocampus 19(12):1247–1253PubMed
go back to reference Yurko-Mauro K, McCarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, Salem N Jr, Stedman M, Investigators M (2010) Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement 6(6):456–464. doi:10.1016/j.jalz.2010.01.013 PubMed Yurko-Mauro K, McCarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, Salem N Jr, Stedman M, Investigators M (2010) Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement 6(6):456–464. doi:10.​1016/​j.​jalz.​2010.​01.​013 PubMed
go back to reference Zerbi V, Jansen D, Dederen PJ, Veltien A, Hamans B, Liu Y, Heerschap A, Kiliaan AJ (2012) Microvascular cerebral blood volume changes in aging APP(swe)/PS1 (dE9) AD mouse model: a voxel-wise approach. Brain Struct Funct. doi:10.1007/s00429-012-0448-8 PubMed Zerbi V, Jansen D, Dederen PJ, Veltien A, Hamans B, Liu Y, Heerschap A, Kiliaan AJ (2012) Microvascular cerebral blood volume changes in aging APP(swe)/PS1 (dE9) AD mouse model: a voxel-wise approach. Brain Struct Funct. doi:10.​1007/​s00429-012-0448-8 PubMed
go back to reference Zhang X, Huang G, Liu H, Chang H, Wilson JX (2012) Folic acid enhances Notch signaling, hippocampal neurogenesis, and cognitive function in a rat model of cerebral ischemia. Nutrition Neurosci 15(2):55–61. doi:10.1179/1476830511Y.0000000025 Zhang X, Huang G, Liu H, Chang H, Wilson JX (2012) Folic acid enhances Notch signaling, hippocampal neurogenesis, and cognitive function in a rat model of cerebral ischemia. Nutrition Neurosci 15(2):55–61. doi:10.​1179/​1476830511Y.​0000000025
go back to reference Zhou Y, Elkins PD, Howell LA, Ryan DH, Harris RB (1998) Apolipoprotein-E deficiency results in an altered stress responsiveness in addition to an impaired spatial memory in young mice. Brain Res 788(1–2):151–159PubMed Zhou Y, Elkins PD, Howell LA, Ryan DH, Harris RB (1998) Apolipoprotein-E deficiency results in an altered stress responsiveness in addition to an impaired spatial memory in young mice. Brain Res 788(1–2):151–159PubMed
go back to reference Zhou B, Teramukai S, Fukushima M (2007) Prevention and treatment of dementia or Alzheimer’s disease by statins: a meta-analysis. Dement Geriatr Cogn Disord 23(3):194–201PubMed Zhou B, Teramukai S, Fukushima M (2007) Prevention and treatment of dementia or Alzheimer’s disease by statins: a meta-analysis. Dement Geriatr Cogn Disord 23(3):194–201PubMed
Metadata
Title
Impact of a multi-nutrient diet on cognition, brain metabolism, hemodynamics, and plasticity in apoE4 carrier and apoE knockout mice
Authors
Diane Jansen
Valerio Zerbi
Carola I. F. Janssen
Daan van Rooij
Bastian Zinnhardt
Pieter J. Dederen
Alan J. Wright
Laus M. Broersen
Dieter Lütjohann
Arend Heerschap
Amanda J. Kiliaan
Publication date
01-09-2014
Publisher
Springer Berlin Heidelberg
Published in
Brain Structure and Function / Issue 5/2014
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-013-0606-7

Other articles of this Issue 5/2014

Brain Structure and Function 5/2014 Go to the issue