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Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases
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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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“Additionally, astrocytes supply cholesterol to neurons through the transport of apolipoprotein E (APOE) particles (Vance, 2012).”
From Sterol dysregulation in Smith–Lemli–Opitz syndrome causes astrocyte immune reactivity through microglia crosstalk (2022) · cites this paper as Vance, 2012
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“since astrocytes supplement neuronal cholesterol through lipoprotein transfer45,46.”
From A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome (2013) · cites this paper as [46]
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ApoE4-carrying Human Astrocytes Oversupply Cholesterol into Neurons and Promote Aβ GenerationPreprint
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Contribution of Dietary Fat in Neuroinflammation
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Metadata
- 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
- 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
- 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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