Top

Published in:

Open Access 01-08-2017 | Review Article

Cholesterol as a modifying agent of the neurovascular unit structure and function under physiological and pathological conditions

Authors: Ewelina Czuba, Aleksandra Steliga, Grażyna Lietzau, Przemysław Kowiański

Published in: Metabolic Brain Disease | Issue 4/2017

Abstract

The brain, demanding constant level of cholesterol, precisely controls its synthesis and homeostasis. The brain cholesterol pool is almost completely separated from the rest of the body by the functional blood-brain barrier (BBB). Only a part of cholesterol pool can be exchanged with the blood circulation in the form of the oxysterol metabolites such, as 27-hydroxycholesterol (27-OHC) and 24S–hydroxycholesterol (24S–OHC). Not only neurons but also blood vessels and neuroglia, constituting neurovascular unit (NVU), are crucial for the brain cholesterol metabolism and undergo precise regulation by numerous modulators, metabolites and signal molecules. In physiological conditions maintaining the optimal cholesterol concentration is important for the energetic metabolism, composition of cell membranes and myelination. However, a growing body of evidence indicates the consequences of the cholesterol homeostasis dysregulation in several pathophysiological processes. There is a causal relationship between hypercholesterolemia and 1) development of type 2 diabetes due to long-term high-fat diet consumption, 2) significance of the oxidative stress consequences for cerebral amyloid angiopathy and neurodegenerative diseases, 3) insulin resistance on progression of the neurodegenerative brain diseases. In this review, we summarize the current state of knowledge concerning the cholesterol influence upon functioning of the NVU under physiological and pathological conditions.

Abbott NJ, Rönnbäck L, Hansson E (2006) Astrocyte–endothelial interactions at the blood–brain barrier. Nat Rev Neurosci 7:41–53. doi:10.1038/nrn1824 CrossRefPubMed

Abildayeva K, Jansen PJ, Hirsch-Reinshagen V et al (2006) 24(S)-hydroxycholesterol participates in a liver X receptor-controlled pathway in astrocytes that regulates apolipoprotein E-mediated cholesterol efflux. J Biol Chem 281:12799–12808. doi:10.1074/jbc.M601019200 CrossRefPubMed

Anderson R, Barnes JC, Bliss TVP et al (1998) Behavioural, physiological and morphological analysis of a line of apolipoprotein E knockout mouse. Neuroscience 85:93–110. doi:10.1016/S0306-4522(97)00598-8 CrossRefPubMed

Apelt J, Schliebs R (2001) β-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology. Brain Res 894:21–30. doi:10.1016/S0006-8993(00)03176-0 CrossRefPubMed

Arnold SE, Lucki I, Brookshire BR et al (2014) High fat diet produces brain insulin resistance, synaptodendritic abnormalities and altered behavior in mice. Neurobiol Dis 67:79–87. doi:10.1016/j.nbd.2014.03.011 CrossRefPubMedPubMedCentral

Asahina M, Yoshiyama Y, Hattori T (2001) Expression of matrix metalloproteinase-9 and urinary-type plasminogen activator in Alzheimer’s disease brain. Clin Neuropathol 20:60–63PubMed

Aytan N, Jung T, Tamtürk F et al (2008) Oxidative stress related changes in the brain of hypercholesterolemic rabbits. Biofactors 33:225–236. doi:10.1002/biof.5520330308 CrossRefPubMed

Balazs Z, Panzenboeck U, Hammer A et al (2004) Uptake and transport of high-density lipoprotein (HDL) and HDL-associated alpha-tocopherol by an in vitro blood-brain barrier model. J Neurochem 89:939–950. doi:10.1111/j.1471-4159.2004.02373.x CrossRefPubMed

Björkhem I (2006) Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med 260:493–508CrossRefPubMed

Björkhem I, Leoni V, Meaney S (2010) Genetic connections between neurological disorders and cholesterol metabolism. J Lipid Res 51:2489–2503. doi:10.1194/jlr.R006338 CrossRefPubMedPubMedCentral

Bogdanovic N, Bretillon L, Lund EG et al (2001) On the turnover of brain cholesterol in patients with Alzheimer’s disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells. Neurosci Lett 314:45–48. doi:10.1016/S0304-3940(01)02277-7 CrossRefPubMed

Bosco D, Fava A, Plastino M et al (2011) Possible implications of insulin resistance and glucose metabolism in Alzheimer’s disease pathogenesis. J Cell Mol Med 15:1807–1821CrossRefPubMedPubMedCentral

Brown MS, Goldstein JL (1999) A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc Natl Acad Sci U S A 96:11041–11048. doi:10.1073/pnas.96.20.11041 CrossRefPubMedPubMedCentral

Brown J, Theisler C, Silberman S et al (2004) Differential expression of cholesterol hydroxylases in Alzheimer’s disease. J Biol Chem 279:34674–34681. doi:10.1074/jbc.M402324200 CrossRefPubMed

Cao D, Lu H, Lewis TL, Li N (2007) Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease. J Biol Chem 282:36275–36282. doi:10.1074/jbc.M703561200 CrossRefPubMed

Castellano JM, Kim J, Stewart FR et al (2011) Human apoE isoforms differentially regulate brain amyloid-β peptide clearance. Sci Transl Med 3:89ra57. doi:10.1126/scitranslmed.3002156 CrossRefPubMedPubMedCentral

Chen YL, Wang LM, Chen Y et al (2016) Changes in astrocyte functional markers and β-amyloid metabolism-related proteins in the early stages of hypercholesterolemia. Neuroscience 316:178–191. doi:10.1016/j.neuroscience.2015.12.039 CrossRefPubMed

Chen J, Zhang X, Kusumo H et al (2013) Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis. Biochim Biophys Acta - Mol Cell Biol Lipids 1831:263–275. doi:10.1016/j.bbalip.2012.09.007 CrossRef

Chung W-S, Verghese PB, Chakraborty C et al (2016) Novel allele-dependent role for {APOE} in controlling the rate of synapse pruning by astrocytes. Proc Natl Acad Sci U S A 113:10186–10191. doi:10.1073/pnas.1609896113 CrossRefPubMedPubMedCentral

Corder EH, Saunders AM, Strittmatter WJ et al (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261:921–923. doi:10.1126/science.8346443 CrossRefPubMed

Crawford A, Fassett RG, Geraghty DP et al (2012) Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease. Gene 501:89–103CrossRefPubMed

de Oliveira J, Moreira ELG, dos Santos DB et al (2014) Increased susceptibility to amyloid-β-induced neurotoxicity in mice lacking the low-density lipoprotein receptor. J Alzheimers Dis 41:43–60. doi:10.3233/JAD-132228 PubMed

Dietschy JM, Turley SD (2004) Thematic review series: brain lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J Lipid Res 45:1375–1397. doi:10.1194/jlr.R400004-JLR200 CrossRefPubMed

Dringen R (2000) Metabolism and functions of glutathione in brain. Prog Neurobiol 62:649–671. doi:10.1016/S0301-0082(99)00060-X CrossRefPubMed

Edwards PA, Kennedy MA, Mak PA (2002) LXRs; oxysterol-activated nuclear receptors that regulate genes controlling lipid homeostasis. Vasc Pharmacol 38:249–256. doi:10.1016/S1537-1891(02)00175-1 CrossRef

Ehehalt R, Keller P, Haass C et al (2003) Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts. J Cell Biol 160:113–123. doi:10.1083/jcb.200207113 CrossRefPubMedPubMedCentral

Faraco G, Sugiyama Y, Lane D et al (2016) Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension. J Clin Invest 126:4674–4689. doi:10.1172/JCI86950 CrossRefPubMedPubMedCentral

Farris W, Mansourian S, Chang Y et al (2003) Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci U S A 100:4162–4167. doi:10.1073/pnas.0230450100 CrossRefPubMedPubMedCentral

Gaylor J (2002) Membrane-bound enzymes of cholesterol synthesis from lanosterol. Biochem Biophys Res Commun 1146:1139–1146. doi:10.1006/2001.2008 CrossRef

Ghosh S, Wu MD, Shaftel SS et al (2013) Sustained interleukin-1β overexpression exacerbates tau pathology despite reduced amyloid burden in an Alzheimer’s mouse model. J Neurosci 33:5053–5064. doi:10.1523/JNEUROSCI.4361-12.2013 CrossRefPubMedPubMedCentral

Ghribi O, Larsen B, Schrag M, Herman MM (2006) High cholesterol content in neurons increases BACE, β-amyloid, and phosphorylated tau levels in rabbit hippocampus. Exp Neurol 200:460–467. doi:10.1016/j.expneurol.2006.03.019 CrossRefPubMed

Gosselet F, Saint-Pol J, Fenart L (2014) Effects of oxysterols on the blood-brain barrier: implications for Alzheimer’s disease. Biochem Biophys Res Commun 446:687–691CrossRefPubMed

Han X, Chen M, Wang F et al (2013) Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice. Cell Stem Cell 12:342–353. doi:10.1016/j.stem.2012.12.015 CrossRefPubMedPubMedCentral

Hawkes CA, Gentleman SM, Nicoll JA, Carare RO (2015) Prenatal high-fat diet alters the cerebrovasculature and clearance of β-amyloid in adult offspring. J Pathol 235:619–631. doi:10.1002/path.4468 CrossRefPubMed

Hawkes CA, Sullivan PM, Hands S et al (2012) Disruption of arterial perivascular drainage of amyloid-β from the brains of mice expressing the human APOE ε4 allele. PLoS One 7:e41636. doi:10.1371/journal.pone.0041636 CrossRefPubMedPubMedCentral

Hayashi H, Campenot RB, Vance DE, Vance JE (2004) Glial lipoproteins stimulate axon growth of central nervous system neurons in compartmented cultures. J Biol Chem 279:14009–14015. doi:10.1074/jbc.M313828200 CrossRefPubMed

Herz J (2009) Apolipoprotein E receptors in the nervous system. Curr Opin Lipidol 20:190–196. doi:10.1097/MOL.0b013e32832d3a10 CrossRefPubMedPubMedCentral

Herzig MC, Winkler DT, Burgermeister P et al (2004) Aβ is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis. Nat Neurosci 7:954–960. doi:10.1038/nn1302 CrossRefPubMed

Hirrlinger J, König J, Keppler D et al (2001) The multidrug resistance protein MRP1 mediates the release of glutathione disulfide from rat astrocytes during oxidative stress. J Neurochem 76:627–636. doi:10.1046/j.1471-4159.2001.00101.x CrossRefPubMed

Hirsch-Reinshagen V, Zhou S, Burgess BL et al (2004) Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain. J Biol Chem 279:41197–41207. doi:10.1074/jbc.M407962200 CrossRefPubMed

Hohnholt MC, Dringen R (2014) Short time exposure to hydrogen peroxide induces sustained glutathione export from cultured neurons. Free Radic Biol Med 70:33–44. doi:10.1016/j.freeradbiomed.2014.02.005 CrossRefPubMed

Hughes TM, Kuller LH, Lopez OL et al (2012) Markers of cholesterol metabolism in the brain show stronger associations with cerebrovascular disease than Alzheimer’s disease. J Alzheimers Dis 30:53–61. doi:10.3233/JAD-2012-111460 PubMedPubMedCentral

Iadecola C, Nedergaard M (2007) Glial regulation of the cerebral microvasculature. Nat Neurosci 10:1369–1376. doi:10.1038/nn2003 CrossRefPubMed

Iliff JJ, Wang M, Liao Y, et al (2012) A Paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, Including Amyloid β. Sci Transl Med 4:147ra111. doi:10.1126/scitranslmed.3003748

Jansen PJ, Lütjohann D, Thelen KM et al (2009) Absence of ApoE upregulates murine brain ApoD and ABCA1 levels, but does not affect brain sterol levels, while human ApoE3 and human ApoE4 upregulate brain cholesterol precursor levels. J Alzheimers Dis 18:319–329. doi:10.3233/JAD-2009-1150 CrossRefPubMed

Kim WS, Guillemin GJ, Glaros EN et al (2006) Quantitation of ATP-binding cassette subfamily-a transporter gene expression in primary human brain cells. Neuroreport 17:891–896. doi:10.1097/01.wnr.0000221833.41340.cd CrossRefPubMed

Kim WS, Rahmanto AS, Kamili A et al (2007) Role of ABCG1 and ABCA1 in regulation of neuronal cholesterol efflux to apolipoprotein E discs and suppression of amyloid-β peptide generation. J Biol Chem 282:2851–2861. doi:10.1074/jbc.M607831200 CrossRefPubMed

Kowiański P, Lietzau G, Steliga A et al (2013) The astrocytic contribution to neurovascular coupling – still more questions than answers? Neurosci Res 75:171–183. doi:10.1016/j.neures.2013.01.014 CrossRefPubMed

Lahiri DK (2004) Apolipoprotein E as a target for developing new therapeutics for Alzheimer’s disease based on studies from protein, RNA, and regulatory region of the gene. J Mol Neurosci 23:225–233. doi:10.1385/JMN:23:3:225 CrossRefPubMed

Lehtinen MK, Bjornsson CS, Dymecki SM et al (2013) The choroid plexus and cerebrospinal fluid: emerging roles in development, disease, and therapy. J Neurosci 33:17553–17559. doi:10.1523/JNEUROSCI.3258-13.2013 CrossRefPubMedPubMedCentral

Levi O, Lütjohann D, Devir A et al (2005) Regulation of hippocampal cholesterol metabolism by apoE and environmental stimulation. J Neurochem 95:987–997. doi:10.1111/j.1471-4159.2005.03441.x CrossRefPubMed

Liao WL, Heo GY, Dodder NG, et al (2011) Quantification of cholesterol-metabolizing p450s CYP27A1 and CYP46A1 in neural tissues reveals a lack of enzyme-product correlations in human retina but not human brain. J Proteome Res 10:241–248. doi:10.1021/pr1008898

Liu J-P, Tang Y, Zhou S et al (2010a) Cholesterol involvement in the pathogenesis of neurodegenerative diseases. Mol Cell Neurosci 43:33–42. doi:10.1016/j.mcn.2009.07.013 CrossRefPubMed

Liu Q, Trotter J, Zhang J et al (2010b) Neuronal LRP1 knockout in adult mice leads to impaired brain lipid metabolism and progressive, age-dependent synapse loss and neurodegeneration. J Neurosci 30:17068–17078. doi:10.1523/JNEUROSCI.4067-10.2010 CrossRefPubMedPubMedCentral

Lütjohann D, Papassotiropoulos A, Björkhem I et al (2000) Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients. J Lipid Res 41:195–198PubMed

Mahley RW, Rall SC (2000) APOLIPOPROTEIN E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 1:507–537. doi:10.1146/annurev.genom.1.1.507 CrossRefPubMed

Martiskainen H, Haapasalo A, Kurkinen KM et al (2013) Targeting ApoE4/ApoE receptor LRP1 in Alzheimer’s disease. Expert Opin Ther Targets 17:781–794. doi:10.1517/14728222.2013.789862 CrossRefPubMed

Mashayekhi F, Hadavi M, Vaziri HR, Naji M (2010) Increased acidic fibroblast growth factor concentrations in the serum and cerebrospinal fluid of patients with Alzheimer’s disease. J Clin Neurosci 17:357–359. doi:10.1016/j.jocn.2009.05.037 CrossRefPubMed

Matsuda A, Nagao K, Matsuo M et al (2013) 24(S)-hydroxycholesterol is actively eliminated from neuronal cells by ABCA1. J Neurochem 126:93–101. doi:10.1111/jnc.12275 CrossRefPubMed

Milionis HJ, Florentin M, Giannopoulos S (2008) Metabolic syndrome and Alzheimer’s disease: a link to a vascular hypothesis? CNS Spectr 13:606–613CrossRefPubMed

Morell P, Jurevics H (1996) Origin of cholesterol in myelin. Neurochem Res 21:463–470. doi:10.1007/BF02527711 CrossRefPubMed

Nagayasu Y, Morita SY, Hayashi H et al (2014) Increasing cellular level of phosphatidic acid enhances FGF-1 production in long term-cultured rat astrocytes. Brain Res 1563:31–40. doi:10.1016/j.brainres.2014.03.035 CrossRefPubMed

Nieweg K, Schaller H, Pfrieger FW (2009) Marked differences in cholesterol synthesis between neurons and glial cells from postnatal rats. J Neurochem 109:125–134. doi:10.1111/j.1471-4159.2009.05917.x CrossRefPubMed

Oberheim NA, Takano T, Han X et al (2009) Uniquely hominid features of adult human astrocytes. J Neurosci 29:3276–3287. doi:10.1523/JNEUROSCI.4707-08.2009 CrossRefPubMedPubMedCentral

Oram JF, Heinecke JW (2005) ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular disease. Physiol Rev 85:1343–1372. doi:10.1152/physrev.00005.2005 CrossRefPubMed

Orth M, Bellosta S (2012) Cholesterol: its regulation and role in central nervous system disorders. Cholesterol 2012:1–19. doi:10.1155/2012/292598 CrossRef

Papassotiropoulos A, Lutjohann D, Bagli M et al (2000) Plasma 24S-hydroxycholesterol: a peripheral indicator of neuronal degeneration and potential state marker for Alzheimer’s disease. Neuroreport 11:1959–1962. doi:10.1016/S0197-4580(00)82775-X CrossRefPubMed

Patrone C, Eriksson O, Lindholm D (2014) Diabetes drugs and neurological disorders: new views and therapeutic possibilities. Lancet Diabetes Endocrinol 2:256–262. doi:10.1016/S2213-8587(13)70125-6 CrossRefPubMed

Pfrieger FW, Ungerer N (2011) Cholesterol metabolism in neurons and astrocytes. Prog Lipid Res 50:357–371CrossRefPubMed

Riddell DR, Zhou H, Comery TA et al (2007) The LXR agonist TO901317 selectively lowers hippocampal Aβ42 and improves memory in the Tg2576 mouse model of Alzheimer’s disease. Mol Cell Neurosci 34:621–628. doi:10.1016/j.mcn.2007.01.011 CrossRefPubMed

Róg T, Stimson LM, Pasenkiewicz-Gierula M et al (2008) Replacing the cholesterol hydroxyl group with the ketone group facilitates sterol flip-flop and promotes membrane fluidity. J Phys Chem B 112:1946–1952. doi:10.1021/jp075078h CrossRefPubMed

Ross GW, O’Callaghan JP, Sharp DS et al (2003) Quantification of regional glial fibrillary acidic protein levels in Alzheimer’s disease. Acta Neurol Scand 107:318–323CrossRefPubMed

Russell DW, Halford RW, Ramirez DMO et al (2009) Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain. Annu Rev Biochem 78:1017–1040. doi:10.1146/annurev.biochem.78.072407.103859 CrossRefPubMedPubMedCentral

Saeed AA, Genové G, Li T et al (2014) Effects of a disrupted blood-brain barrier on cholesterol homeostasis in the brain. J Biol Chem 289:23712–23722. doi:10.1074/jbc.M114.556159 CrossRefPubMedPubMedCentral

Sagara J, Makino N, Bannai S (1996) Glutathione efflux from cultured astrocytes. J Neurochem 66:1876–1881. doi:10.1046/j.1471-4159.1996.66051876.x CrossRefPubMed

Saher G, Brügger B, Lappe-Siefke C et al (2005) High cholesterol level is essential for myelin membrane growth. Nat Neurosci 8:468–475. doi:10.1038/nn1426 PubMed

Shin HK, Jones PB, Garcia-Alloza M et al (2007) Age-dependent cerebrovascular dysfunction in a transgenic mouse model of cerebral amyloid angiopathy. Brain 130:2310–2319. doi:10.1093/brain/awm156 CrossRefPubMed

Stapleton PA, James ME, Goodwill AG, Frisbee JC (2008) Obesity and vascular dysfunction. Pathophysiology 15:79–89. doi:10.1016/j.pathophys.2008.04.007 CrossRefPubMedPubMedCentral

Strickland DK, Au DT, Cunfer P, Muratoglu SC (2014) Low-density lipoprotein receptor-related protein-1: role in the regulation of vascular integrity. Arterioscler Thromb Vasc Biol 34:487–498CrossRefPubMedPubMedCentral

Sucher NJ, Lipton SA (1991) Redox modulatory site of the NMDA receptor-channel complex: regulation by oxidized glutathione. J Neurosci Res 30:582–591. doi:10.1002/jnr.490300316 CrossRefPubMed

Sun Y, Wu S, Bu G et al (1998) Glial fibrillary acidic protein-apolipoprotein E (apoE) transgenic mice: astrocyte-specific expression and differing biological effects of astrocyte-secreted apoE3 and apoE4 lipoproteins. J Neurosci 18:3261–3272PubMed

Thirumangalakudi L, Samany PG, Owoso A et al (2006) Angiogenic proteins are expressed by brain blood vessels in Alzheimer’s disease. J Alzheimers Dis 10:111–118CrossRefPubMed

Torp R, Danbolt NC, Babaie E et al (1994) Differential expression of two glial glutamate transporters in the rat brain: in situ hybridization study. Eur J Neurosci 6:936–942CrossRefPubMed

Vance JE (2006) Lipid imbalance in the neurological disorder, Niemann-pick C disease. FEBS Lett 580:5518–5524CrossRefPubMed

Vance JE, Hayashi H (2010) Formation and function of apolipoprotein E-containing lipoproteins in the nervous system. Biochim Biophys Acta - Mol Cell Biol Lipids 1801:806–818CrossRef

Vance JE, Pan D, Campenot RB et al (1994) Evidence that the major membrane lipids, except cholesterol, are made in axons of cultured rat sympathetic neurons. J Neurochem 62:329–337. doi:10.1046/j.1471-4159.1994.62010329.x CrossRefPubMed

Wahrle SE, Jiang H, Parsadanian M et al (2005) Deletion of Abca1 increases Abeta deposition in the PDAPP transgenic mouse model of Alzheimer disease. J Biol Chem 280:43236–43242. doi:10.1074/jbc.M508780200 CrossRefPubMed

Wahrle SE, Jiang H, Parsadanian M et al (2008) Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J Clin Invest 118:671–682. doi:10.1172/JCI33622 PubMedPubMedCentral

Weller RO, Subash M, Preston SD et al (2008) Clearance of Aβ from the brain in Alzheimer’s disease: perivascular drainage of amyloid-β peptides from the brain and its failure in cerebral amyloid Angiopathy and Alzheimer’s disease: perivascular drainage of Aβ peptides and cerebral amyloid Angiopathy. Brain Pathol 18:253–266. doi:10.1111/j.1750-3639.2008.00133.x CrossRefPubMed

William Rebeck G, Reiter JS, Strickland DK, Hyman BT (1993) Apolipoprotein E in sporadic Alzheimer’s disease: allelic variation and receptor interactions. Neuron 11:575–580. doi:10.1016/0896-6273(93)90070-8 CrossRef

Xiao M, Hu G (2014) Involvement of aquaporin 4 in astrocyte function and neuropsychiatric disorders. CNS Neurosci Ther 20:385–390CrossRefPubMed

Xu PT, Gilbert JR, Qiu HL et al (1999) Specific regional transcription of apolipoprotein E in human brain neurons. Am J Pathol 154:601–611. doi:10.1016/S0002-9440(10)65305-9 CrossRefPubMedPubMedCentral

Xu Z, Xiao N, Chen Y et al (2015) Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits. Mol Neurodegener 10:58. doi:10.1186/s13024-015-0056-1 CrossRefPubMedPubMedCentral

Yan P, Hu X, Song H et al (2006) Matrix metalloproteinase-9 degrades amyloid-β fibrils in vitro and compact plaques in situ. J Biol Chem 281:24566–24574. doi:10.1074/jbc.M602440200 CrossRefPubMed

Yao X, Hrabetova S, Nicholson C, Manley GT (2008) Aquaporin-4-deficient mice have increased extracellular space without tortuosity change. J Neurosci 28:5460–5464. doi:10.1523/JNEUROSCI.0257-08.2008 CrossRefPubMedPubMedCentral

Ye B, Shen H, Zhang J et al (2015) Dual pathways mediate β-amyloid stimulated glutathione release from astrocytes. Glia 63:2208–2219. doi:10.1002/glia.22886 CrossRefPubMed

Zambón D, Quintana M, Mata P et al (2010) Higher incidence of mild cognitive impairment in familial hypercholesterolemia. Am J Med 123:267–274. doi:10.1016/j.amjmed.2009.08.015 CrossRefPubMedPubMedCentral

Zelcer N, Khanlou N, Clare R et al (2007) Attenuation of neuroinflammation and Alzheimer’s disease pathology by liver x receptors. Proc Natl Acad Sci U S A 104:10601–10606. doi:10.1073/pnas.0701096104 CrossRefPubMedPubMedCentral

Zhang C, Rodriguez C, Spaulding J et al (2012) Age-dependent and tissue-related glutathione redox status in a mouse model of Alzheimer’s disease. J Alzheimers Dis 28:655–666. doi:10.3233/JAD-2011-111244 PubMedPubMedCentral

Zhang Y, Sloan SA, Clarke LE et al (2016) Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron 89:37–53. doi:10.1016/j.neuron.2015.11.013 CrossRefPubMed

Zlokovic BV (2008) The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57:178–201CrossRefPubMed

Zlokovic BV (2011) Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 12:723–738. doi:10.1038/nrn3114 PubMedPubMedCentral

Title: Cholesterol as a modifying agent of the neurovascular unit structure and function under physiological and pathological conditions
Authors: Ewelina Czuba
Aleksandra Steliga
Grażyna Lietzau
Przemysław Kowiański
Publication date: 01-08-2017
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 4/2017
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-017-0015-3

At a glance: The STEP trials

Springer Medicine

Cholesterol as a modifying agent of the neurovascular unit structure and function under physiological and pathological conditions

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2017

Synergistic anticonvulsant effects of pregabalin and amlodipine on acute seizure model of epilepsy in mice

Late onset MELAS with m.3243A > G mutation and its association with aneurysm formation

Identification of novel ATP7A mutations and prenatal diagnosis in Chinese patients with Menkes disease

Brain heparan sulphate proteoglycans are altered in developing foetus when exposed to in-utero hyperglycaemia

The analgesic effect of trans-resveratrol is regulated by calcium channels in the hippocampus of mice

Analysis of estrogen receptor β gene methylation in autistic males in a Chinese Han population