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

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

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

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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Authors
Vance, J. E.
Affiliations
University of Alberta (CA)
Corresponding author
Vance, Jean E.
Venue
Disease Models & Mechanisms
Published
2012-01-01
Volume
5
Issue
6
Pages
746-55
ISSN
  • 1754-8403 (ISSN-L)
  • 1754-8411
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
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
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Health Sciences › Medicine › Physiology › 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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