Cited by 164Cholesterol and Lipid MetabolismAlzheimer's disease research and treatmentsLipoproteins and Cardiovascular Health

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Apolipoprotein E and cholesterol in aging and disease in the brain

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de Chaves, Elena Posse, Narayanaswami, Vasanthy, Christoffersen, Christina, Nielsen, Lars Bo·2008·Future Lipidology

DOI 10.2217/17460875.3.5.505PMC PMC2600507

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Abstract

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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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
ORCID: 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)
DOI: 10.2217/17460875.3.5.505
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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Apolipoprotein E and cholesterol in aging and disease in the brain

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