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Published in: Acta Neuropathologica 5/2014

01-05-2014 | Original Paper

CSF Apo-E levels associate with cognitive decline and MRI changes

Authors: Jon B. Toledo, Xiao Da, Michael W. Weiner, David A. Wolk, Sharon X. Xie, Steven E. Arnold, Christos Davatzikos, Leslie M. Shaw, John Q. Trojanowski, For the Alzheimer’s Disease Neuroimaging Initiative

Published in: Acta Neuropathologica | Issue 5/2014

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Abstract

Apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for Alzheimer’s disease (AD) and it is thought to do so by modulating levels of its product, apolipoprotein E (Apo-E), and regulating amyloid-β (Aβ) clearance. However, information on clinical and biomarker correlates of Apo-E proteins is scarce. We examined the relationship of cerebrospinal fluid (CSF) and plasma Apo-E protein levels, and APOE genotype to cognition and AD biomarker changes in 311 AD neuroimaging initiative subjects with CSF Apo-E measurements and 565 subjects with plasma Apo-E measurements. At baseline, higher CSF Apo-E levels were associated with higher total and phosphorylated CSF tau levels. CSF Apo-E levels were associated with longitudinal cognitive decline, MCI conversion to dementia, and gray matter atrophy rate in total tau/Aβ1–42 ratio and APOE genotype-adjusted analyses. In analyses stratified by APOE genotype, our results were only significant in the group without the ε4 allele. Baseline CSF Apo-E levels did not predict longitudinal CSF Aβ or tau changes. Plasma Apo-E levels show a mild correlation with CSF Apo-E levels, but were not associated with longitudinal cognitive and MRI changes. Based on our analyses, we speculate that increased CSF Apo-E2 or -E3 levels might represent a protective response to injury in AD and may have neuroprotective effects by decreasing neuronal damage independent of tau and amyloid deposition in addition to its effects on amyloid clearance.
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Literature
3.
go back to reference Boschert U, Merlo-Pich E, Higgins G, Roses AD, Catsicas S (1999) Apolipoprotein E expression by neurons surviving excitotoxic stress. Neurobiol Dis 6(6):508–514. doi:10.1006/nbdi 1999.0251PubMedCrossRef Boschert U, Merlo-Pich E, Higgins G, Roses AD, Catsicas S (1999) Apolipoprotein E expression by neurons surviving excitotoxic stress. Neurobiol Dis 6(6):508–514. doi:10.​1006/​nbdi 1999.0251PubMedCrossRef
4.
go back to reference Boyles JK, Pitas RE, Wilson E, Mahley RW, Taylor JM (1985) Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system. J Clin Invest 76(4):1501–1513. doi:10.1172/JCI112130 PubMedCentralPubMedCrossRef Boyles JK, Pitas RE, Wilson E, Mahley RW, Taylor JM (1985) Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system. J Clin Invest 76(4):1501–1513. doi:10.​1172/​JCI112130 PubMedCentralPubMedCrossRef
5.
go back to reference Bunce D, Fratiglioni L, Small BJ, Winblad B, Backman L (2004) APOE and cognitive decline in preclinical Alzheimer disease and non-demented aging. Neurology 63(5):816–821PubMedCrossRef Bunce D, Fratiglioni L, Small BJ, Winblad B, Backman L (2004) APOE and cognitive decline in preclinical Alzheimer disease and non-demented aging. Neurology 63(5):816–821PubMedCrossRef
6.
go back to reference Burnham SC, Faux NG, Wilson W, Laws SM, Ames D, Bedo J, Bush AI, Doecke JD, Ellis KA, Head R, Jones G, Kiiveri H, Martins RN, Rembach A, Rowe CC, Salvado O, Macaulay SL, Masters CL, Villemagne VL (2013) A blood-based predictor for neocortical Abeta burden in Alzheimer’s disease: results from the AIBL study. Mol Psychiatry. doi:10.1038/mp.2013.40 Burnham SC, Faux NG, Wilson W, Laws SM, Ames D, Bedo J, Bush AI, Doecke JD, Ellis KA, Head R, Jones G, Kiiveri H, Martins RN, Rembach A, Rowe CC, Salvado O, Macaulay SL, Masters CL, Villemagne VL (2013) A blood-based predictor for neocortical Abeta burden in Alzheimer’s disease: results from the AIBL study. Mol Psychiatry. doi:10.​1038/​mp.​2013.​40
7.
go back to reference Castellano JM, Kim J, Stewart FR, Jiang H, DeMattos RB, Patterson BW, Fagan AM, Morris JC, Mawuenyega KG, Cruchaga C, Goate AM, Bales KR, Paul SM, Bateman RJ, Holtzman DM (2011) Human apoE isoforms differentially regulate brain amyloid-beta peptide clearance. Sci Transl Med 3(89):89ra57. doi:10.1126/scitranslmed.3002156 PubMedCentralPubMedCrossRef Castellano JM, Kim J, Stewart FR, Jiang H, DeMattos RB, Patterson BW, Fagan AM, Morris JC, Mawuenyega KG, Cruchaga C, Goate AM, Bales KR, Paul SM, Bateman RJ, Holtzman DM (2011) Human apoE isoforms differentially regulate brain amyloid-beta peptide clearance. Sci Transl Med 3(89):89ra57. doi:10.​1126/​scitranslmed.​3002156 PubMedCentralPubMedCrossRef
8.
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):921–923PubMedCrossRef 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):921–923PubMedCrossRef
10.
go back to reference Cramer PE, Cirrito JR, Wesson DW, Lee CY, Karlo JC, Zinn AE, Casali BT, Restivo JL, Goebel WD, James MJ, Brunden KR, Wilson DA, Landreth GE (2012) ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models. Science 335(6075):1503–1506. doi:10.1126/science.1217697 PubMedCentralPubMedCrossRef Cramer PE, Cirrito JR, Wesson DW, Lee CY, Karlo JC, Zinn AE, Casali BT, Restivo JL, Goebel WD, James MJ, Brunden KR, Wilson DA, Landreth GE (2012) ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models. Science 335(6075):1503–1506. doi:10.​1126/​science.​1217697 PubMedCentralPubMedCrossRef
11.
go back to reference Cruchaga C, Kauwe JS, Nowotny P, Bales K, Pickering EH, Mayo K, Bertelsen S, Hinrichs A, Fagan AM, Holtzman DM, Morris JC, Goate AM (2012) Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer’s disease. Hum Mol Genet 21(20):4558–4571. doi:10.1093/hmg/dds296 PubMedCentralPubMedCrossRef Cruchaga C, Kauwe JS, Nowotny P, Bales K, Pickering EH, Mayo K, Bertelsen S, Hinrichs A, Fagan AM, Holtzman DM, Morris JC, Goate AM (2012) Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer’s disease. Hum Mol Genet 21(20):4558–4571. doi:10.​1093/​hmg/​dds296 PubMedCentralPubMedCrossRef
12.
13.
go back to reference Doecke JD, Laws SM, Faux NG, Wilson W, Burnham SC, Lam CP, Mondal A, Bedo J, Bush AI, Brown B, De Ruyck K, Ellis KA, Fowler C, Gupta VB, Head R, Macaulay SL, Pertile K, Rowe CC, Rembach A, Rodrigues M, Rumble R, Szoeke C, Taddei K, Taddei T, Trounson B, Ames D, Masters CL, Martins RN (2012) Blood-based protein biomarkers for diagnosis of Alzheimer disease. Arch Neurol 69(10):1318–1325. doi:10.1001/archneurol2012.1282 PubMedCrossRef Doecke JD, Laws SM, Faux NG, Wilson W, Burnham SC, Lam CP, Mondal A, Bedo J, Bush AI, Brown B, De Ruyck K, Ellis KA, Fowler C, Gupta VB, Head R, Macaulay SL, Pertile K, Rowe CC, Rembach A, Rodrigues M, Rumble R, Szoeke C, Taddei K, Taddei T, Trounson B, Ames D, Masters CL, Martins RN (2012) Blood-based protein biomarkers for diagnosis of Alzheimer disease. Arch Neurol 69(10):1318–1325. doi:10.​1001/​archneurol2012.​1282 PubMedCrossRef
14.
go back to reference Donkin JJ, Stukas S, Hirsch-Reinshagen V, Namjoshi D, Wilkinson A, May S, Chan J, Fan J, Collins J, Wellington CL (2010) ATP-binding cassette transporter A1 mediates the beneficial effects of the liver X receptor agonist GW3965 on object recognition memory and amyloid burden in amyloid precursor protein/presenilin 1 mice. J Biol Chem 285(44):34144–34154. doi:10.1074/jbc.M110.108100 PubMedCentralPubMedCrossRef Donkin JJ, Stukas S, Hirsch-Reinshagen V, Namjoshi D, Wilkinson A, May S, Chan J, Fan J, Collins J, Wellington CL (2010) ATP-binding cassette transporter A1 mediates the beneficial effects of the liver X receptor agonist GW3965 on object recognition memory and amyloid burden in amyloid precursor protein/presenilin 1 mice. J Biol Chem 285(44):34144–34154. doi:10.​1074/​jbc.​M110.​108100 PubMedCentralPubMedCrossRef
15.
go back to reference Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278(16):1349–1356PubMedCrossRef Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278(16):1349–1356PubMedCrossRef
16.
go back to reference Figurski MJ, Waligorska T, Toledo J, Vanderstichele H, Korecka M, Lee VM, Trojanowski JQ, Shaw LM (2012) Improved protocol for measurement of plasma beta-amyloid in longitudinal evaluation of Alzheimer’s disease neuroimaging initiative study patients. Alzheimers Dement 8(4):250–260. doi:10.1016/j.jalz.2012.01.001 PubMedCentralPubMedCrossRef Figurski MJ, Waligorska T, Toledo J, Vanderstichele H, Korecka M, Lee VM, Trojanowski JQ, Shaw LM (2012) Improved protocol for measurement of plasma beta-amyloid in longitudinal evaluation of Alzheimer’s disease neuroimaging initiative study patients. Alzheimers Dement 8(4):250–260. doi:10.​1016/​j.​jalz.​2012.​01.​001 PubMedCentralPubMedCrossRef
18.
go back to reference Foster JK, Albrecht MA, Savage G, Lautenschlager NT, Ellis KA, Maruff P, Szoeke C, Taddei K, Martins R, Masters CL, Ames D (2013) Lack of reliable evidence for a distinctive {varepsilon}4-related cognitive phenotype that is independent from clinical diagnostic status: findings from the Australian imaging, biomarkers and lifestyle study. Brain 136(Pt 7):2201–2216. doi:10.1093/brain/awt127 PubMedCrossRef Foster JK, Albrecht MA, Savage G, Lautenschlager NT, Ellis KA, Maruff P, Szoeke C, Taddei K, Martins R, Masters CL, Ames D (2013) Lack of reliable evidence for a distinctive {varepsilon}4-related cognitive phenotype that is independent from clinical diagnostic status: findings from the Australian imaging, biomarkers and lifestyle study. Brain 136(Pt 7):2201–2216. doi:10.​1093/​brain/​awt127 PubMedCrossRef
19.
go back to reference Fukuyama R, Mizuno T, Mori S, Yanagisawa K, Nakajima K, Fushiki S (2000) Age-dependent decline in the apolipoprotein E level in cerebrospinal fluid from control subjects and its increase in cerebrospinal fluid from patients with Alzheimer’s disease. Eur Neurol 43(3):161–169 (8157)PubMedCrossRef Fukuyama R, Mizuno T, Mori S, Yanagisawa K, Nakajima K, Fushiki S (2000) Age-dependent decline in the apolipoprotein E level in cerebrospinal fluid from control subjects and its increase in cerebrospinal fluid from patients with Alzheimer’s disease. Eur Neurol 43(3):161–169 (8157)PubMedCrossRef
21.
go back to reference Gupta VB, Laws SM, Villemagne VL, Ames D, Bush AI, Ellis KA, Lui JK, Masters C, Rowe CC, Szoeke C, Taddei K, Martins RN (2011) Plasma apolipoprotein E and Alzheimer disease risk: the AIBL study of aging. Neurology 76(12):1091–1098. doi:10.1212/WNL.0b013e318211c352 PubMedCrossRef Gupta VB, Laws SM, Villemagne VL, Ames D, Bush AI, Ellis KA, Lui JK, Masters C, Rowe CC, Szoeke C, Taddei K, Martins RN (2011) Plasma apolipoprotein E and Alzheimer disease risk: the AIBL study of aging. Neurology 76(12):1091–1098. doi:10.​1212/​WNL.​0b013e318211c352​ PubMedCrossRef
22.
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):13–17. doi:10.1136/jnnp.2008.150433 PubMedCrossRef 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):13–17. doi:10.​1136/​jnnp.​2008.​150433 PubMedCrossRef
23.
go back to reference Hong Z, Shi M, Chung KA, Quinn JF, Peskind ER, Galasko D, Jankovic J, Zabetian CP, Leverenz JB, Baird G, Montine TJ, Hancock AM, Hwang H, Pan C, Bradner J, Kang UJ, Jensen PH, Zhang J (2010) DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain 133(Pt 3):713–726. doi:10.1093/brain/awq008 PubMedCentralPubMedCrossRef Hong Z, Shi M, Chung KA, Quinn JF, Peskind ER, Galasko D, Jankovic J, Zabetian CP, Leverenz JB, Baird G, Montine TJ, Hancock AM, Hwang H, Pan C, Bradner J, Kang UJ, Jensen PH, Zhang J (2010) DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain 133(Pt 3):713–726. doi:10.​1093/​brain/​awq008 PubMedCentralPubMedCrossRef
24.
go back to reference Hu WT, Holtzman DM, Fagan AM, Shaw LM, Perrin R, Arnold SE, Grossman M, Xiong C, Craig-Schapiro R, Clark CM, Pickering E, Kuhn M, Chen Y, Van Deerlin VM, McCluskey L, Elman L, Karlawish J, Chen-Plotkin A, Hurtig HI, Siderowf A, Swenson F, Lee VM, Morris JC, Trojanowski JQ, Soares H (2012) Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease. Neurology 79(9):897–905. doi:10.1212/WNL.0b013e318266fa70 PubMedCentralPubMedCrossRef Hu WT, Holtzman DM, Fagan AM, Shaw LM, Perrin R, Arnold SE, Grossman M, Xiong C, Craig-Schapiro R, Clark CM, Pickering E, Kuhn M, Chen Y, Van Deerlin VM, McCluskey L, Elman L, Karlawish J, Chen-Plotkin A, Hurtig HI, Siderowf A, Swenson F, Lee VM, Morris JC, Trojanowski JQ, Soares H (2012) Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease. Neurology 79(9):897–905. doi:10.​1212/​WNL.​0b013e318266fa70​ PubMedCentralPubMedCrossRef
26.
27.
go back to reference Jack CR Jr, Bernstein MA, Fox NC, Thompson P, Alexander G, Harvey D, Borowski B, Britson PJ, Whitwell JL, Ward C, Dale AM, Felmlee JP, Gunter JL, Hill DL, Killiany R, Schuff N, Fox-Bosetti S, Lin C, Studholme C, DeCarli CS, Krueger G, Ward HA, Metzger GJ, Scott KT, Mallozzi R, Blezek D, Levy J, Debbins JP, Fleisher AS, Albert M, Green R, Bartzokis G, Glover G, Mugler J, Weiner MW (2008) The Alzheimer’s disease neuroimaging initiative (ADNI): MRI methods. J Magn Reson Imaging 27(4):685–691. doi:10.1002/jmri.21049 PubMedCentralPubMedCrossRef Jack CR Jr, Bernstein MA, Fox NC, Thompson P, Alexander G, Harvey D, Borowski B, Britson PJ, Whitwell JL, Ward C, Dale AM, Felmlee JP, Gunter JL, Hill DL, Killiany R, Schuff N, Fox-Bosetti S, Lin C, Studholme C, DeCarli CS, Krueger G, Ward HA, Metzger GJ, Scott KT, Mallozzi R, Blezek D, Levy J, Debbins JP, Fleisher AS, Albert M, Green R, Bartzokis G, Glover G, Mugler J, Weiner MW (2008) The Alzheimer’s disease neuroimaging initiative (ADNI): MRI methods. J Magn Reson Imaging 27(4):685–691. doi:10.​1002/​jmri.​21049 PubMedCentralPubMedCrossRef
29.
go back to reference Kim S, Swaminathan S, Inlow M, Risacher SL, Nho K, Shen L, Foroud TM, Petersen RC, Aisen PS, Soares H, Toledo JB, Shaw LM, Trojanowski JQ, Weiner MW, McDonald BC, Farlow MR, Ghetti B, Saykin AJ (2013) Influence of genetic variation on plasma protein levels in older adults using a multi-analyte panel. PLoS One 8(7):e70269. doi:10.1371/journal.pone.0070269 PubMedCentralPubMedCrossRef Kim S, Swaminathan S, Inlow M, Risacher SL, Nho K, Shen L, Foroud TM, Petersen RC, Aisen PS, Soares H, Toledo JB, Shaw LM, Trojanowski JQ, Weiner MW, McDonald BC, Farlow MR, Ghetti B, Saykin AJ (2013) Influence of genetic variation on plasma protein levels in older adults using a multi-analyte panel. PLoS One 8(7):e70269. doi:10.​1371/​journal.​pone.​0070269 PubMedCentralPubMedCrossRef
30.
go back to reference Korff A, Liu C, Ginghina C, Shi M, Zhang J (2013) α-Synuclein in cerebrospinal fluid of Alzheimer’s disease and mild cognitive impairment. J Alzheimers Dis 36(4):679–688. doi:10.3233/JAD-130458 Korff A, Liu C, Ginghina C, Shi M, Zhang J (2013) α-Synuclein in cerebrospinal fluid of Alzheimer’s disease and mild cognitive impairment. J Alzheimers Dis 36(4):679–688. doi:10.​3233/​JAD-130458
32.
go back to reference Landreth GE, Cramer PE, Lakner MM, Cirrito JR, Wesson DW, Brunden KR, Wilson DA (2013) Response to comments on “ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models”. Science 340(6135):924-g. doi:10.1126/science.1234114 PubMedCrossRef Landreth GE, Cramer PE, Lakner MM, Cirrito JR, Wesson DW, Brunden KR, Wilson DA (2013) Response to comments on “ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models”. Science 340(6135):924-g. doi:10.​1126/​science.​1234114 PubMedCrossRef
33.
go back to reference Lehtimaki T, Pirttila T, Mehta PD, Wisniewski HM, Frey H, Nikkari T (1995) Apolipoprotein E (apoE) polymorphism and its influence on ApoE concentrations in the cerebrospinal fluid in Finnish patients with Alzheimer’s disease. Hum Genet 95(1):39–42PubMed Lehtimaki T, Pirttila T, Mehta PD, Wisniewski HM, Frey H, Nikkari T (1995) Apolipoprotein E (apoE) polymorphism and its influence on ApoE concentrations in the cerebrospinal fluid in Finnish patients with Alzheimer’s disease. Hum Genet 95(1):39–42PubMed
36.
go back to reference Poirier J, Hess M, May PC, Finch CE (1991) Astrocytic apolipoprotein E mRNA and GFAP mRNA in hippocampus after entorhinal cortex lesioning. Brain Res Mol Brain Res 11(2):97–106PubMedCrossRef Poirier J, Hess M, May PC, Finch CE (1991) Astrocytic apolipoprotein E mRNA and GFAP mRNA in hippocampus after entorhinal cortex lesioning. Brain Res Mol Brain Res 11(2):97–106PubMedCrossRef
37.
go back to reference Price AR, Xu G, Siemienski ZB, Smithson LA, Borchelt DR, Golde TE, Felsenstein KM (2013) Comment on “ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models”. Science 340(6135):924-d. doi:10.1126/science.1234089 PubMedCrossRef Price AR, Xu G, Siemienski ZB, Smithson LA, Borchelt DR, Golde TE, Felsenstein KM (2013) Comment on “ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models”. Science 340(6135):924-d. doi:10.​1126/​science.​1234089 PubMedCrossRef
38.
go back to reference Reiman EM, Chen K, Liu X, Bandy D, Yu M, Lee W, Ayutyanont N, Keppler J, Reeder SA, Langbaum JB, Alexander GE, Klunk WE, Mathis CA, Price JC, Aizenstein HJ, DeKosky ST, Caselli RJ (2009) Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc Natl Acad Sci USA 106(16):6820–6825. doi:10.1073/pnas.0900345106 PubMedCentralPubMedCrossRef Reiman EM, Chen K, Liu X, Bandy D, Yu M, Lee W, Ayutyanont N, Keppler J, Reeder SA, Langbaum JB, Alexander GE, Klunk WE, Mathis CA, Price JC, Aizenstein HJ, DeKosky ST, Caselli RJ (2009) Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc Natl Acad Sci USA 106(16):6820–6825. doi:10.​1073/​pnas.​0900345106 PubMedCentralPubMedCrossRef
41.
go back to reference Riddell DR, Zhou H, Atchison K, Warwick HK, Atkinson PJ, Jefferson J, Xu L, Aschmies S, Kirksey Y, Hu Y, Wagner E, Parratt A, Xu J, Li Z, Zaleska MM, Jacobsen JS, Pangalos MN, Reinhart PH (2008) Impact of apolipoprotein E (ApoE) polymorphism on brain ApoE levels. J Neurosci 28(45):11445–11453. doi:10.1523/JNEUROSCI.1972-08.2008 PubMedCrossRef Riddell DR, Zhou H, Atchison K, Warwick HK, Atkinson PJ, Jefferson J, Xu L, Aschmies S, Kirksey Y, Hu Y, Wagner E, Parratt A, Xu J, Li Z, Zaleska MM, Jacobsen JS, Pangalos MN, Reinhart PH (2008) Impact of apolipoprotein E (ApoE) polymorphism on brain ApoE levels. J Neurosci 28(45):11445–11453. doi:10.​1523/​JNEUROSCI.​1972-08.​2008 PubMedCrossRef
43.
go back to reference Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, Blennow K, Soares H, Simon A, Lewczuk P, Dean R, Siemers E, Potter W, Lee VM, Trojanowski JQ (2009) Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol 65(4):403–413. doi:10.1002/ana.21610 PubMedCentralPubMedCrossRef Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, Blennow K, Soares H, Simon A, Lewczuk P, Dean R, Siemers E, Potter W, Lee VM, Trojanowski JQ (2009) Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol 65(4):403–413. doi:10.​1002/​ana.​21610 PubMedCentralPubMedCrossRef
44.
go back to reference Shaw LM, Vanderstichele H, Knapik-Czajka M, Figurski M, Coart E, Blennow K, Soares H, Simon AJ, Lewczuk P, Dean RA, Siemers E, Potter W, Lee VM, Trojanowski JQ (2011) Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI. Acta Neuropathol 121(5):597–609. doi:10.1007/s00401-011-0808-0 PubMedCentralPubMedCrossRef Shaw LM, Vanderstichele H, Knapik-Czajka M, Figurski M, Coart E, Blennow K, Soares H, Simon AJ, Lewczuk P, Dean RA, Siemers E, Potter W, Lee VM, Trojanowski JQ (2011) Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI. Acta Neuropathol 121(5):597–609. doi:10.​1007/​s00401-011-0808-0 PubMedCentralPubMedCrossRef
47.
go back to reference Soares HD, Potter WZ, Pickering E, Kuhn M, Immermann FW, Shera DM, Ferm M, Dean RA, Simon AJ, Swenson F, Siuciak JA, Kaplow J, Thambisetty M, Zagouras P, Koroshetz WJ, Wan HI, Trojanowski JQ, Shaw LM (2012) Plasma biomarkers associated with the apolipoprotein E genotype and Alzheimer disease. Arch Neurol 69(10):1310–1317. doi:10.1001/archneurol2012.1070 PubMedCentralPubMedCrossRef Soares HD, Potter WZ, Pickering E, Kuhn M, Immermann FW, Shera DM, Ferm M, Dean RA, Simon AJ, Swenson F, Siuciak JA, Kaplow J, Thambisetty M, Zagouras P, Koroshetz WJ, Wan HI, Trojanowski JQ, Shaw LM (2012) Plasma biomarkers associated with the apolipoprotein E genotype and Alzheimer disease. Arch Neurol 69(10):1310–1317. doi:10.​1001/​archneurol2012.​1070 PubMedCentralPubMedCrossRef
48.
go back to reference Tesseur I, Lo AC, Roberfroid A, Dietvorst S, Van Broeck B, Borgers M, Gijsen H, Moechars D, Mercken M, Kemp J, D’Hooge R, De Strooper B (2013) Comment on “ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models”. Science 340(6135):924-e. doi:10.1126/science.1233937 PubMedCrossRef Tesseur I, Lo AC, Roberfroid A, Dietvorst S, Van Broeck B, Borgers M, Gijsen H, Moechars D, Mercken M, Kemp J, D’Hooge R, De Strooper B (2013) Comment on “ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models”. Science 340(6135):924-e. doi:10.​1126/​science.​1233937 PubMedCrossRef
49.
go back to reference Toledo JB, Arnold SE, Raible K, Brettschneider J, Xie SX, Grossman M, Monsell SE, Kukull WA, Trojanowski JQ (2013) Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain 136(Pt 9):2697–2706. doi:10.1093/brain/awt188 PubMedCrossRef Toledo JB, Arnold SE, Raible K, Brettschneider J, Xie SX, Grossman M, Monsell SE, Kukull WA, Trojanowski JQ (2013) Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain 136(Pt 9):2697–2706. doi:10.​1093/​brain/​awt188 PubMedCrossRef
50.
go back to reference Toledo JB, Korff A, Shaw LM, Trojanowski JQ, Zhang J (2013) CSF alpha-synuclein improves diagnostic and prognostic performance of CSF tau and Abeta in Alzheimer’s disease. Acta Neuropathol 126(5):683–697. doi:10.1007/s00401-013-1148-z PubMedCrossRef Toledo JB, Korff A, Shaw LM, Trojanowski JQ, Zhang J (2013) CSF alpha-synuclein improves diagnostic and prognostic performance of CSF tau and Abeta in Alzheimer’s disease. Acta Neuropathol 126(5):683–697. doi:10.​1007/​s00401-013-1148-z PubMedCrossRef
52.
go back to reference Toledo JB, Vanderstichele H, Figurski M, Aisen PS, Petersen RC, Weiner MW, Jack CR Jr, Jagust W, Decarli C, Toga AW, Toledo E, Xie SX, Lee VM, Trojanowski JQ, Shaw LM (2011) Factors affecting Abeta plasma levels and their utility as biomarkers in ADNI. Acta Neuropathol 122(4):401–413. doi:10.1007/s00401-011-0861-8 PubMedCentralPubMedCrossRef Toledo JB, Vanderstichele H, Figurski M, Aisen PS, Petersen RC, Weiner MW, Jack CR Jr, Jagust W, Decarli C, Toga AW, Toledo E, Xie SX, Lee VM, Trojanowski JQ, Shaw LM (2011) Factors affecting Abeta plasma levels and their utility as biomarkers in ADNI. Acta Neuropathol 122(4):401–413. doi:10.​1007/​s00401-011-0861-8 PubMedCentralPubMedCrossRef
54.
go back to reference Vanmierlo T, Rutten K, Dederen J, Bloks VW, van Vark-van der Zee LC, Kuipers F, Kiliaan A, Blokland A, Sijbrands EJ, Steinbusch H, Prickaerts J, Lutjohann D, Mulder M (2011) Liver X receptor activation restores memory in aged AD mice without reducing amyloid. Neurobiol Aging 32(7):1262–1272. doi:10.1016/j.neurobiolaging.2009.07.005 PubMedCrossRef Vanmierlo T, Rutten K, Dederen J, Bloks VW, van Vark-van der Zee LC, Kuipers F, Kiliaan A, Blokland A, Sijbrands EJ, Steinbusch H, Prickaerts J, Lutjohann D, Mulder M (2011) Liver X receptor activation restores memory in aged AD mice without reducing amyloid. Neurobiol Aging 32(7):1262–1272. doi:10.​1016/​j.​neurobiolaging.​2009.​07.​005 PubMedCrossRef
55.
go back to reference Veeraraghavalu K, Zhang C, Miller S, Hefendehl JK, Rajapaksha TW, Ulrich J, Jucker M, Holtzman DM, Tanzi RE, Vassar R, Sisodia SS (2013) Comment on “ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models”. Science 340(6135):924-f. doi:10.1126/science.1235505 PubMedCrossRef Veeraraghavalu K, Zhang C, Miller S, Hefendehl JK, Rajapaksha TW, Ulrich J, Jucker M, Holtzman DM, Tanzi RE, Vassar R, Sisodia SS (2013) Comment on “ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models”. Science 340(6135):924-f. doi:10.​1126/​science.​1235505 PubMedCrossRef
56.
go back to reference Vijayaraghavan S, Maetzler W, Reimold M, Lithner CU, Liepelt-Scarfone I, Berg D, Darreh-Shori T (2013) High apolipoprotein E in cerebrospinal fluid of patients with Lewy body disorders is associated with dementia. Alzheimers Dement. doi:10.1016/j.jalz.2013.03.010 PubMed Vijayaraghavan S, Maetzler W, Reimold M, Lithner CU, Liepelt-Scarfone I, Berg D, Darreh-Shori T (2013) High apolipoprotein E in cerebrospinal fluid of patients with Lewy body disorders is associated with dementia. Alzheimers Dement. doi:10.​1016/​j.​jalz.​2013.​03.​010 PubMed
57.
go back to reference Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, Ames D, Rowe CC, Masters CL (2013) Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 12(4):357–367. doi:10.1016/S1474-4422(13)70044-9 PubMedCrossRef Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, Ames D, Rowe CC, Masters CL (2013) Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 12(4):357–367. doi:10.​1016/​S1474-4422(13)70044-9 PubMedCrossRef
58.
59.
go back to reference Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, Green RC, Harvey D, Jack CR, Jagust W, Liu E, Morris JC, Petersen RC, Saykin AJ, Schmidt ME, Shaw L, Siuciak JA, Soares H, Toga AW, Trojanowski JQ (2012) The Alzheimer’s disease neuroimaging initiative: a review of papers published since its inception. Alzheimers Dement 8(1 Suppl):S1–S68. doi:10.1016/j.jalz.2011.09.172 PubMedCentralPubMedCrossRef Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, Green RC, Harvey D, Jack CR, Jagust W, Liu E, Morris JC, Petersen RC, Saykin AJ, Schmidt ME, Shaw L, Siuciak JA, Soares H, Toga AW, Trojanowski JQ (2012) The Alzheimer’s disease neuroimaging initiative: a review of papers published since its inception. Alzheimers Dement 8(1 Suppl):S1–S68. doi:10.​1016/​j.​jalz.​2011.​09.​172 PubMedCentralPubMedCrossRef
60.
go back to reference Weisgraber KH, Shinto LH (1991) Identification of the disulfide-linked homodimer of apolipoprotein E3 in plasma. Impact on receptor binding activity. J Biol Chem 266(18):12029–12034PubMed Weisgraber KH, Shinto LH (1991) Identification of the disulfide-linked homodimer of apolipoprotein E3 in plasma. Impact on receptor binding activity. J Biol Chem 266(18):12029–12034PubMed
61.
go back to reference Winnock M, Letenneur L, Jacqmin-Gadda H, Dallongeville J, Amouyel P, Dartigues JF (2002) Longitudinal analysis of the effect of apolipoprotein E epsilon4 and education on cognitive performance in elderly subjects: the PAQUID study. J Neurol Neurosurg Psychiatry 72(6):794–797PubMedCentralPubMedCrossRef Winnock M, Letenneur L, Jacqmin-Gadda H, Dallongeville J, Amouyel P, Dartigues JF (2002) Longitudinal analysis of the effect of apolipoprotein E epsilon4 and education on cognitive performance in elderly subjects: the PAQUID study. J Neurol Neurosurg Psychiatry 72(6):794–797PubMedCentralPubMedCrossRef
63.
go back to reference Xu Q, Bernardo A, Walker D, Kanegawa T, Mahley RW, Huang Y (2006) Profile and regulation of apolipoprotein E (ApoE) expression in the CNS in mice with targeting of green fluorescent protein gene to the ApoE locus. J Neurosci 26(19):4985–4994. doi:10.1523/JNEUROSCI.5476-05.2006 PubMedCrossRef Xu Q, Bernardo A, Walker D, Kanegawa T, Mahley RW, Huang Y (2006) Profile and regulation of apolipoprotein E (ApoE) expression in the CNS in mice with targeting of green fluorescent protein gene to the ApoE locus. J Neurosci 26(19):4985–4994. doi:10.​1523/​JNEUROSCI.​5476-05.​2006 PubMedCrossRef
64.
go back to reference Yaffe K, Cauley J, Sands L, Browner W (1997) Apolipoprotein E phenotype and cognitive decline in a prospective study of elderly community women. Arch Neurol 54(9):1110–1114PubMedCrossRef Yaffe K, Cauley J, Sands L, Browner W (1997) Apolipoprotein E phenotype and cognitive decline in a prospective study of elderly community women. Arch Neurol 54(9):1110–1114PubMedCrossRef
Metadata
Title
CSF Apo-E levels associate with cognitive decline and MRI changes
Authors
Jon B. Toledo
Xiao Da
Michael W. Weiner
David A. Wolk
Sharon X. Xie
Steven E. Arnold
Christos Davatzikos
Leslie M. Shaw
John Q. Trojanowski
For the Alzheimer’s Disease Neuroimaging Initiative
Publication date
01-05-2014
Publisher
Springer Berlin Heidelberg
Published in
Acta Neuropathologica / Issue 5/2014
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-013-1236-0

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Acknowledgement to Referees

Acknowledgement to referees