The DOI matches its Crossref record; 328 of the 328 references it cites were found in a registry or an index.
Apolipoprotein E and cholesterol in aging and disease in the brain
Open accessAbstract
Cholesterol can be detrimental or vital, and must be present in the right place at the right time and in the right amount. This is well known in the heart and the vascular system. However, in the CNS cholesterol is still an enigma, although several of its fundamental functions in the brain have been identified. Brain cholesterol has attracted additional attention owing to its close connection to ApoE, a key polymorphic transporter of extracellular cholesterol in humans. Indeed, both cholesterol and ApoE are so critical to fundamental activities of the brain, that the brain regulates their synthesis autonomously. Yet, similar control mechanisms of ApoE and cholesterol homeostasis may exist on either sides of the blood-brain barrier. One indication is that the APOE ε4 allele is associated with hypercholesterolemia and a proatherogenic profile on the vascular side and with increased risk of Alzheimer's disease on the CNS side. In this review, we draw attention to the association between cholesterol and ApoE in the aging and diseased brain, and to the behavior of the ApoE4 protein at the molecular level. The attempt to correlate in vivo and in vitro observations is challenging but crucial for developing future strategies to address ApoE-related aberrations in cholesterol metabolism selectively in the brain.
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“Cells harboring PSMC5 variants exhibit characteristics reminiscent of senescent or neurodegenerative cells, including impaired mitophagy47, type I IFN response48, abnormal apolipoproteins and/or cholesterol levels49,50, cognitive inflexibility51,52, impaired neuritogenesis53,54, and an imbalanced E/I ratio55,56.”
From Investigating the neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies (2025) · cites this paper as [50]
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Metadata
- Authors
- de Chaves, E. P., Narayanaswami, V., Christoffersen, C., & Nielsen, L. B.
- Affiliations
- Department of PharmacologyUniversity of Alberta, 928 Medical Sciences BuildingEdmontonAlberta, T6G 2S2, Canada, Tel.: Fax.:
- California State University, Long Beach (US)
- Corresponding author
- Narayanaswami, Vasanthy
- Christoffersen, Christina
- Nielsen, Lars Bo
- Venue
- Future Lipidology
- Publisher
- Informa UK Limited
- Published
- 2008-01-01
- Volume
- 3
- Issue
- 5
- Pages
- 505-530
- ISSN
- 1746-0875 (ISSN-L)
- PMC
- PMC2600507
- OpenAlex
- W2143416920
- Cited by
- 164
- References
- 327
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 4 · 2023: 11 · 2022: 14 · 2021: 22 · 2020: 14 · 2019: 15 · 2018: 9 · 2017: 6 · 2016: 6 · 2015: 5 · 2014: 10 · 2013: 6 · 2012: 10
- FWCI
- 7.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Future Lipidology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL064159)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- apolipoprotein E, APOE ε4, brain cholesterol, cholesterol homeostasis, brain aging, Alzheimer's disease, hypercholesterolemia, atherosclerosis, blood-brain barrier, cholesterol metabolism
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