Cited by 344Cholesterol and Lipid MetabolismLysosomal Storage Disorders ResearchAlzheimer's disease research and treatments

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Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases

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Vance, Jean E.·2012·Disease Models & Mechanisms

DOI 10.1242/dmm.010124PMC PMC3484857

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Abstract

Summary: Dysregulation of cholesterol homeostasis in the brain is increasingly being linked to chronic neurodegenerative disorders, including Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), Niemann-Pick type C (NPC) disease and Smith-Lemli Opitz syndrome (SLOS). However, the molecular mechanisms underlying the correlation between altered cholesterol metabolism and the neurological deficits are, for the most part, not clear. NPC disease and SLOS are caused by mutations in genes involved in the biosynthesis or intracellular trafficking of cholesterol, respectively. However, the types of neurological impairments, and the areas of the brain that are most affected, differ between these diseases. Some, but not all, studies indicate that high levels of plasma cholesterol correlate with increased risk of developing AD. Moreover, inheritance of the E4 isoform of apolipoprotein E (APOE), a cholesterol-carrying protein, markedly increases the risk of developing AD. Whether or not treatment of AD with statins is beneficial remains controversial, and any benefit of statin treatment might be due to anti-inflammatory properties of the drug. Cholesterol balance is also altered in HD and PD, although no causal link between dysregulated cholesterol homeostasis and neurodegeneration has been established. Some important considerations for treatment of neurodegenerative diseases are the impermeability of the blood-brain barrier to many therapeutic agents and difficulties in reversing brain damage that has already occurred. This article focuses on how cholesterol balance in the brain is altered in several neurodegenerative diseases, and discusses some commonalities and differences among the diseases.

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2 retracted

Retracted: Differential effects of 24‐hydroxycholesterol and 27‐hydroxycholesterol on tyrosine hydroxylase and α‐synuclein in human neuroblastoma SH‐SY5Y cells
Prasanthi, J. R. P., Feist, G., Thomasson, S., Thompson, A. J., Schommer, E., & Ghribi, O. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05736.x · Cited by 91
Retracted
RETRACTED: The oxysterol 27‐hydroxycholesterol regulates α‐synuclein and tyrosine hydroxylase expression levels in human neuroblastoma cells through modulation of liver X receptors and estrogen receptors–relevance to Parkinson’s disease
Marwarha, G., Rhen, T., Schommer, T., & Ghribi, O. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07497.x · Cited by 85
Retracted
Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
A Receptor-Mediated Pathway for Cholesterol Homeostasis
Brown, M. S., & Goldstein, J. L. (1986) · Science · doi:10.1126/science.3513311 · Cited by 5,703
Alzheimer's Disease Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920
Statins and the risk of dementia
Jick, H., Zornberg, G. L., Jick, S. S., Seshadri, S. S., & Drachman, D. (2000) · The Lancet · doi:10.1016/s0140-6736(00)03155-x · Cited by 1,764
CNS synaptogenesis promoted by glia-derived cholesterol
Mauch, D. H., Nägler, K., Schumacher, S., Göritz, C., Müller, E.-C., Otto, A., & Pfrieger, F. W. (2001) · Science · doi:10.1126/science.294.5545.1354 · Cited by 1,711
Decreased Prevalence of Alzheimer Disease Associated With 3-Hydroxy-3-Methyglutaryl Coenzyme A Reductase Inhibitors
Wolozin, B. L. (2000) · Archives of Neurology · doi:10.1001/archneur.57.10.1439 · Cited by 1,408
Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease.
Strittmatter, W. J., Weisgraber, K. H., Huang, D. Y., Dong, L. M., Salvesen, G. S., Pericak-Vance, M., Schmechel, D., Saunders, A. M., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.8098 · Cited by 1,363
Cholesterol Modification of Hedgehog Signaling Proteins in Animal Development
Porter, J. A., Young, K. E., & Beachy, P. A. (1996) · Science · doi:10.1126/science.274.5285.255 · Cited by 1,360
Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance
Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., Fagan, A. M., Morris, J. C., Mawuenyega, K. G., Cruchaga, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002156 · Cited by 1,242 · cited 12×
“Importantly, inheritance of the APOE4 allele is the strongest known genetic risk factor for the development of late-onset AD (Corder et al., 1993).”
BackgroundInfluential
Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons
Simons, M., Keller, P., Strooper, B. D., Beyreuther, K. T., Dotti, C. G., & Simons, K. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6460 · Cited by 1,177
Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy
Bu, G. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2620 · Cited by 1,168
Thematic review series: brain lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal
Dietschy, J. M., & Turley, S. D. (2004) · Journal of Lipid Research · doi:10.1194/jlr.r400004-jlr200 · Cited by 1,095
ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models
Cramer, P. E., Cirrito, J. R., Wesson, D. W., Lee, C. Y. D., Karlo, J. C., Zinn, A. E., Casali, B. T., Restivo, J. L., Goebel, W. D., James, M. J., et al. (2012) · Science · doi:10.1126/science.1217697 · Cited by 1,050
Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts
Ehehalt, R., Keller, P., Haass, C., Thiele, C., & Simons, K. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200207113 · Cited by 932
Cholesterol metabolism in the brain
Dietschy, J. M., & Turley, S. D. (2001) · Current Opinion in Lipidology · doi:10.1097/00041433-200104000-00003 · Cited by 906
Differential loss of striatal projection neurons in Huntington disease.
Reiner, A., Albin, R. L., Anderson, K. D., D'Amato, C. J., Penney, J. B., & Young, A. B. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.15.5733 · Cited by 839
Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system.
Boyles, J. K., Pitas, R. E., Wilson, E., Mahley, R. W., & Taylor, J. M. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112130 · Cited by 829
Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the α-secretase ADAM 10
Kojro, E., Gimpl, G., Lammich, S., März, W., & Fahrenholz, F. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081612998 · Cited by 804
Differential Effects of Apolipoproteins E3 and E4 on Neuronal Growth in Vitro
Nathan, B. P., Bellosta, S., Sanan, D. A., Weisgraber, K. H., Mahley, R. W., & Pitas, R. E. (1994) · Science · doi:10.1126/science.8171342 · Cited by 795
A newly recognized syndromeof multiple congenital anomalies
Smith, D. W., Lemli, L., & Opitz, J. M. (1964) · The Journal of Pediatrics · doi:10.1016/s0022-3476(64)80264-x · Cited by 650
Niemann-Pick disease type C
Vanier, M., & Millat, G. (2003) · Clinical Genetics · doi:10.1034/j.1399-0004.2003.00147.x · Cited by 578
Expression of apolipoprotein E during nerve degeneration and regeneration.
Ignatius, M. J., Gebicke‐Haerter, P. J., Skene, J. H. P., Schilling, J., Weisgraber, K. H., Mahley, R. W., & Shooter, E. M. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.4.1125 · Cited by 571
Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides
Koistinaho, M., Lin, S., Wu, X., Esterman, M., Koger, D., Hanson, J., Higgs, R., Liu, F., Malkani, S., Bales, K. R., et al. (2004) · Nature Medicine · doi:10.1038/nm1058 · Cited by 571
Clearing the brain's amyloid cobwebs
Selkoe, D. J. (2001) · Neuron · doi:10.1016/s0896-6273(01)00475-5 · Cited by 541
Switch-like Control of SREBP-2 Transport Triggered by Small Changes in ER Cholesterol: A Delicate Balance
Radhakrishnan, A., Goldstein, J. L., McDonald, J. G., & Brown, M. S. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.10.008 · Cited by 534
ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE
Wahrle, S. E., Jiang, H., Parsadanian, M., Legleiter, J., Han, X., Fryer, J. D., Kowalewski, T., & Holtzman, D. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407963200 · Cited by 474
Malformation syndromes caused by disorders of cholesterol synthesis
Porter, F. D., & Herman, G. E. (2011) · Journal of Lipid Research · doi:10.1194/jlr.r009548 · Cited by 473
The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol
Barrett, P. J., Song, Y., Van Horn, W. D., Hustedt, E. J., Schafer, J. M., Hadziselimovic, A., Beel, A. J., & Sanders, C. R. (2012) · Science · doi:10.1126/science.1219988 · Cited by 467
Induction of Alzheimer-like β-Amyloid Immunoreactivity in the Brains of Rabbits with Dietary Cholesterol
Sparks, D. L., Scheff, S. W., Hunsaker, J. C., Liu, H., Landers, T., & Gross, D. R. (1994) · Experimental Neurology · doi:10.1006/exnr.1994.1044 · Cited by 443
A role for apolipoprotein E, apolipoprotein A-I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve
Boyles, J. K., Zoellner, C. D., Anderson, L. J., Kosik, L. M., Pitas, R. E., Weisgraber, K. H., Hui, D. Y., Mahley, R. W., Gebicke-Haerter, P. J., & Ignatius, M. J. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113943 · Cited by 419
Wild-Type Huntingtin Protects from Apoptosis Upstream of Caspase-3
Rigamonti, D., Bauer, J. H., De‐Fraja, C., Conti, L., Sipione, S., Sciorati, C., Clementi, E., Hackam, A. S., Hayden, M. R., Li, Y., et al. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-10-03705.2000 · Cited by 406
Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3
Sanan, D. A., Weisgraber, K. H., Russell, S. J., Mahley, R. W., Huang, D., Saunders, A., Schmechel, D., Wisniewski, T., Frangione, B., & Roses, A. D. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117407 · Cited by 404
Neurodegeneration in the Central Nervous System of apoE-Deficient Mice
Masliah, E., Mallory, M. E., Ge, N., Alford, M. F., Veinbergs, I., & Roses, A. D. (1995) · Experimental Neurology · doi:10.1006/exnr.1995.1088 · Cited by 402
Deficiency of ABCA1 Impairs Apolipoprotein E Metabolism in Brain
Hirsch-Reinshagen, V., Zhou, S., Burgess, B. L., Bernier, L., McIsaac, S. A., Chan, J. Y., Tansley, G. H., Cohn, J. S., Hayden, M. R., & Wellington, C. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407962200 · Cited by 385
Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1 −/− mouse
Liu, B., Turley, S. D., Burns, D. K., Miller, A. M., Repa, J. J., & Dietschy, J. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810895106 · Cited by 384
Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
Wahrle, S. E., Jiang, H., Parsadanian, M., Kim, J., Li, A., Knoten, A., Jain, S., Hirsch-Reinshagen, V., Wellington, C. L., Bales, K. R., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33622 · Cited by 370 · cited 1×
“Consistent with these findings, overexpression of ABCA1 in AD mice reduced amyloid deposition (Wahrle et al., 2008).”
Result
Cholesterol Modulates α-Secretase Cleavage of Amyloid Precursor Protein
Bodovitz, S., & Klein, W. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.8.4436 · Cited by 359
Blood—Brain Barrier Permeability Precedes Senile Plaque Formation in an Alzheimer Disease Model
UJIIE, M., DICKSTEIN, D. L., CARLOW, D. A., & JEFFERIES, W. A. (2003) · Microcirculation · doi:10.1038/sj.mn.7800212 · Cited by 351
Elevated levels of oxidized cholesterol metabolites in Lewy body disease brains accelerate α-synuclein fibrilization
Bosco, D. A., Fowler, D. M., Zhang, Q., Nieva, J. J., Powers, E. T., Wentworth, P., Lerner, R. A., & Kelly, J. W. (2006) · Nature Chemical Biology · doi:10.1038/nchembio782 · Cited by 349
A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease
Sano, M., Bell, K. L., Galasko, D., Galvin, J. E., Thomas, R. G., van Dyck, C. H., & Aisen, P. S. S. (2011) · Neurology · doi:10.1212/wnl.0b013e318228bf11 · Cited by 347
Deletion of Abca1 Increases Aβ Deposition in the PDAPP Transgenic Mouse Model of Alzheimer Disease
Wahrle, S. E., Jiang, H., Parsadanian, M., Hartman, R. E., Bales, K. R., Paul, S. M., & Holtzman, D. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508780200 · Cited by 325
Cholesterol 24-Hydroxylase: an enzyme of cholesterol turnover in the brain
Russell, D. W., Halford, R. W., Ramirez, D. M. O., Shah, R., & Kotti, T. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.072407.103859 · Cited by 317
The intracellular transport of low density lipoprotein-derived cholesterol is defective in Niemann-Pick type C fibroblasts.
Liscum, L., Ruggiero, R. M., & Faust, J. R. (1989) · The Journal of Cell Biology · doi:10.1083/jcb.108.5.1625 · Cited by 307
Marked differences in cholesterol synthesis between neurons and glial cells from postnatal rats
Nieweg, K., Schaller, H., & Pfrieger, F. W. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05917.x · Cited by 307
Dysfunction of the Cholesterol Biosynthetic Pathway in Huntington's Disease
Valenza, M., Rigamonti, D., Goffredo, D., Zuccato, C., Fenu, S., Jamot, L., Strand, A., Tarditi, A., Woodman, B., Racchi, M., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3355-05.2005 · Cited by 298
Overexpression of Low-Density Lipoprotein Receptor in the Brain Markedly Inhibits Amyloid Deposition and Increases Extracellular Aβ Clearance
Kim, J., Castellano, J. M., Jiang, H., Basak, J. M., Parsadanian, M., Pham, V., Mason, S. M., Paul, S. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.11.013 · Cited by 274 · cited 2×
“, 1997) – have been linked to an increased incidence of AD (Elder et al., 2007; Fryer et al., 2005; Kim et al., 2009).”
Background
Human APOE Isoform-Dependent Effects on Brain β-Amyloid Levels in PDAPP Transgenic Mice
Bales, K. R., Liu, F., Wu, S., Lin, S., Koger, D., DeLong, C., Hansen, J. C., Sullivan, P. M., & Paul, S. M. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.0887-09.2009 · Cited by 274
A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma
Jiang, X., Sidhu, R., Porter, F. D., Yanjanin, N. M., Speak, A. O., Vruchte, D. T., Platt, F. M., Fujiwara, H., Scherrer, D. E., Zhang, J., et al. (2011) · Journal of Lipid Research · doi:10.1194/jlr.d015735 · Cited by 270
Endocytosis of beta-cyclodextrins is responsible for cholesterol reduction in Niemann-Pick type C mutant cells
Rosenbaum, A. I., Zhang, G., Warren, J. D., & Maxfield, F. R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914309107 · Cited by 267
Apolipoprotein E exhibits isoform‐specific promotion of lipid efflux from astrocytes and neurons in culture
Michikawa, M., Fan, Q., Isobe, I., & Yanagisawa, K. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0741008.x · Cited by 244 · cited 1×
“In this manner, cholesterol is shuttled from astrocytes to neurons (Mauch et al., 2001; Michikawa et al., 2000; Vance and Hayashi, 2010).”
Background
The LDL Receptor Gene Family
Herz, J. (2001) · Neuron · doi:10.1016/s0896-6273(01)00234-3 · Cited by 238
The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease
Hirsch-Reinshagen, V., Maia, L. F., Burgess, B. L., Blain, J.-F., Naus, K. E., McIsaac, S. A., Parkinson, P. F., Chan, J. Y., Tansley, G. H., Hayden, M. R., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508781200 · Cited by 233
Oxysterols as biomarkers in neurodegenerative diseases
Leoni, V., & Caccia, C. (2011) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2011.04.002 · Cited by 229
Cholesterol Level and Statin Use in Alzheimer Disease
Shepardson, N. E. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.203 · Cited by 228
Patterned Purkinje cell degeneration in mouse models of Niemann‐Pick type C disease
Sarna, J. R., Larouche, M., Marzban, H., Sillitoe, R. V., Rancourt, D. E., & Hawkes, R. B. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10522 · Cited by 223
Update on Statins: 2003
Vaughan, C. J., & Gotto, A. M. (2004) · Circulation · doi:10.1161/01.cir.0000139312.10076.ba · Cited by 220
Identification of Surface Residues on Niemann-Pick C2 Essential for Hydrophobic Handoff of Cholesterol to NPC1 in Lysosomes
Wang, M. L., Motamed, M., Infante, R. E., Abi-Mosleh, L., Kwon, H. J., Brown, M. S., & Goldstein, J. L. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.05.016 · Cited by 214
Adeno-associated Virus Gene Therapy With Cholesterol 24-Hydroxylase Reduces the Amyloid Pathology Before or After the Onset of Amyloid Plaques in Mouse Models of Alzheimer's Disease
Hudry, E., Dam, D. V., Kulik, W., Deyn, P. P. D., Stet, F. S., Ahouansou, O., Benraiss, A., Delacourte, A., Bougneres, P. F., Aubourg, P. R., et al. (2009) · Molecular Therapy · doi:10.1038/mt.2009.175 · Cited by 214
Role of Lipoproteins in the Delivery of Lipids to Axons during Axonal Regeneration
de Chaves, E. I. P., Rusiñol, A. E., Vance, D. E., Campenot, R. B., & Vance, J. E. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.49.30766 · Cited by 209
Self-citation
ACAT1 gene ablation increases 24(S)-hydroxycholesterol content in the brain and ameliorates amyloid pathology in mice with AD
Bryleva, E. Y., Rogers, M. A., Chang, C. C. Y., Buen, F., Harris, B. T., Rousselet, E., Seidah, N. G., Oddo, S., LaFerla, F. M., Spencer, T. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913828107 · Cited by 209
Total cholesterol and the risk of Parkinson disease
Hu, G., Antikaínen, R., Jousilahti, P., Kivipelto, M., & Tuomilehto, J. (2008) · Neurology · doi:10.1212/01.wnl.0000312511.62699.a8 · Cited by 205
Serum Cholesterol Levels and the Risk of Parkinson's Disease
de Lau, L. M. L., Koudstaal, P. J., Albert Hofman, D., & Breteler, M. M. B. (2006) · American Journal of Epidemiology · doi:10.1093/aje/kwj283 · Cited by 205
Glial Lipoproteins Stimulate Axon Growth of Central Nervous System Neurons in Compartmented Cultures
Hayashi, H., Campenot, R. B., Vance, D. E., & Vance, J. E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313828200 · Cited by 197
Self-citation
Lower low‐density lipoprotein cholesterol levels are associated with Parkinson's disease
Huang, X., Chen, H., Miller, W. C., Mailman, R. B., Woodard, J. L., Chen, P., Xiang, D., Murrow, R. W., Wang, Y., & Poole, C. (2006) · Movement Disorders · doi:10.1002/mds.21290 · Cited by 190
Cholesterol Level and Statin Use in Alzheimer Disease
Shepardson, N. E. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.242 · Cited by 190
Apolipoprotein E promotes β-amyloid trafficking and degradation by modulating microglial cholesterol levels
Lee, C. Y. D., Tse, W., Smith, J. D., & Landreth, G. E. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.295451 · Cited by 178 · cited 1×
“Some of the mechanisms proposed for A degradation are discussed below (reviewed by Grimm et al., 2012; Lee et al., 2012; Tan and Evin, 2012).”
Background
Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse
Quan, G., Xie, C., Dietschy, J. M., & Turley, S. D. (2003) · Developmental Brain Research · doi:10.1016/j.devbrainres.2003.09.015 · Cited by 177
Postnatal development of inflammation in a murine model of Niemann–Pick type C disease: immunohistochemical observations of microglia and astroglia
Baudry, M., Yao, Y., Simmons, D. A., Liu, J., & Bi, X. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00345-5 · Cited by 174
Presenilin Redistribution Associated with Aberrant Cholesterol Transport Enhances β-Amyloid ProductionIn Vivo
Burns, M. P., Gaynor, K., Olm, V., Mercken, M. H., LaFrancois, J. J., Wang, L., Mathews, P. M., Noble, W. J., Matsuoka, Y., & Duff, K. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-13-05645.2003 · Cited by 173
Reducing Human Apolipoprotein E Levels Attenuates Age-Dependent Aβ Accumulation in Mutant Human Amyloid Precursor Protein Transgenic Mice
Bien-Ly, N., Gillespie, A. K., Walker, D., Yoon, S. Y., & Huang, Y. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0033-12.2012 · Cited by 170
Statins reduce neuronal α‐synuclein aggregation in in vitro models of Parkinson’s disease
Bar‐On, P., Crews, L. A., Koob, A. O., Mizuno, H., Adame, A., Spencer, B. J., & Masliah, E. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05254.x · Cited by 169
Cholesterol Defect Is Marked across Multiple Rodent Models of Huntington's Disease and Is Manifest in Astrocytes
Valenza, M., Leoni, V., Karasinska, J. M., Petricca, L., Fan, J., Carroll, J., Pouladi, M. A., Fossale, E., Nguyen, H. P., Riess, O., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0917-10.2010 · Cited by 166
Functions of lipoprotein receptors in neurons
Beffert, U., Stolt-Bergner, P. C., & Herz, J. (2004) · Journal of Lipid Research · doi:10.1194/jlr.r300017-jlr200 · Cited by 164
Unesterified Cholesterol Accumulation in Late Endosomes/Lysosomes Causes Neurodegeneration and Is Prevented by Driving Cholesterol Export from This Compartment
Aqul, A. A., Liu, B., Ramírez, C. M., Pieper, A. A., Estill, S. J., Burns, D. K., Liu, B., Repa, J. J., Turley, S. D., & Dietschy, J. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.1317-11.2011 · Cited by 157
Oxysterols and Alzheimer's disease
Björkhem, I., Heverin, M., Leoni, V., Meaney, S., & Diczfalusy, U. (2006) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2006.00684.x · Cited by 155
Formation and function of apolipoprotein E-containing lipoproteins in the nervous system
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Veinbergs, I., Jung, M. W., Young, S. J., Uden, E. V., Groves, P. M., & Masliah, E. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00399-1 · Cited by 42
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Porter, F. D. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29872 · Cited by 37
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Herz, J. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01768-9 · Cited by 22
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Longenberger, J., & Shah, Z. A. (2011) · Current Alzheimer Research · doi:10.2174/156720511795745393 · Cited by 21
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Brain lipidomics: From functional landscape to clinical significance
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NPC1 regulates ER contacts with endocytic organelles to mediate cholesterol egress
Höglinger, D., Burgoyne, T., Sanchez-Heras, E., Hartwig, P., Colaco, A., Newton, J., Futter, C. E., Spiegel, S., Platt, F. M., & Eden, E. R. (2019) · Nature Communications · doi:10.1038/s41467-019-12152-2 · Cited by 299
Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes
Habchi, J., Chia, S., Galvagnion, C., Michaels, T. C. T., Bellaiche, M. M. J., Ruggeri, F. S., Sanguanini, M., Idini, I., Kumita, J. R., Sparr, E., et al. (2018) · Nature Chemistry · doi:10.1038/s41557-018-0031-x · Cited by 249

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Authors: Vance, J. E.
Affiliations: University of Alberta (CA)
Corresponding author: Vance, Jean E.
Venue: Disease Models & Mechanisms
Publisher: The Company of Biologists
Published: 2012-01-01
Volume: 5
Issue: 6
Pages: 746-55
ISSN: 1754-8403 (ISSN-L)
1754-8411
DOI: 10.1242/dmm.010124
PMC: PMC3484857
OpenAlex: W2166069871
Cited by: 342
References: 123
Citations by year: 2026: 2 · 2025: 13 · 2024: 26 · 2023: 33 · 2022: 27 · 2021: 37 · 2020: 34 · 2019: 29 · 2018: 24 · 2017: 24 · 2016: 18 · 2015: 28 · 2014: 31 · 2013: 15 · 2012: 1
FWCI: 4.64
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/2.0/ (am, 3425 d)
Locations: Disease Models & Mechanisms (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
HighWire Press Open Archive (submittedVersion)
Funders: Canadian Institutes of Health Research
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords: cholesterol homeostasis, brain cholesterol metabolism, neurodegenerative diseases, Alzheimer's disease, Huntington's disease, Parkinson's disease, Niemann-Pick disease type C, Smith-Lemli-Opitz syndrome, apolipoprotein E, APOE ε4, statins, blood-brain barrier, cholesterol biosynthesis, cholesterol transport
MeSH terms: Animals, Brain, Cholesterol, Humans, Models, Biological, Neurodegenerative Diseases

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Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases

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