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ole of apoE/Aβ Interactions in the Pathogenesis of Alzheimer's Disease and Cerebral Amyloid Angiopathy
Abstract
The epsilon4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). The mechanism underlying this increased risk is not completely clear, yet mounting evidence supports the idea that the ability of apoE to interact with the amyloid-beta (Abeta) peptide and influence its conformation and clearance plays a major role. Evidence to support this concept comes from in vitro and in vivo studies of apoE/Abeta interactions and the effects of these interactions on Abeta conformation and cellular clearance. Recent studies on the effect of murine and human apoE in APP transgenic mice provide direct evidence that apoE is critically involved in the in vivo converstion of Abeta into forms which contain high 5-sheet content and associated cellular toxicity (neuritic plaques and CAA). These studies also suggest a role for human apoE in Abeta clearance in vivo.
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apoE is synthesized mainly by astrocytes and plays an isoform-dependent role in modulating Aβ fibrillization and clearance.
“apoE is synthesized mainly by astrocytes and plays an isoform-dependent role in modulating Aβ fibrillization and clearance (Holtzman, 2001; Zlokovic et al., 2005; Kim et al., 2009).”
From Mechanisms Underlying the Rapid Peroxisome Proliferator-Activated Receptor-γ-Mediated Amyloid Clearance and Reversal of Cognitive Deficits in a Murine Model of Alzheimer's Disease (2012) · cites this paper as Holtzman, 2001
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Amyloid Beta: Structure, Biology and Structure-Based Therapeutic Development
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Role of Ion Channels in Alzheimer’s Disease Pathophysiology
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Metadata
- Authors
- Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Holtzman, David M.
- ORCID
- Holtzman, David M.
- Venue
- Journal of Molecular Neuroscience
- Published
- 2001
- Volume
- 17
- Issue
- 2
- Pages
- 147-155
- ISSN
- 0895-8696 (ISSN-L)
- OpenAlex
- W2004324219
- Cited by
- 143
- References
- 19
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 10 · 2020: 9 · 2019: 3 · 2018: 6 · 2017: 3 · 2016: 2 · 2015: 7 · 2014: 7 · 2013: 11 · 2012: 4
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese Academy of Agricultural Sciences
- National Institutes of Health
- National Institute on Aging (AG11355, AG 05681, P50AG005681, AG13956, P01AG011355)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E, APOE ε4, amyloid-beta, Alzheimer's disease, cerebral amyloid angiopathy, amyloid-beta clearance, APP transgenic mice, neuritic plaques, amyloid-beta oligomerization
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Disease Models, Animal, Humans, Mice, Transgenic, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Protein Structure, Secondary, Molecular Chaperones, Genetic Predisposition to Disease, Mice
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