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Apolipoprotein E and Alzheimer's disease: the influence of apolipoprotein E on amyloid-β and other amyloidogenic proteins
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as the most significant genetic risk factor for late-onset AD, which accounts for >99% of cases. The apoE protein is hypothesized to affect AD pathogenesis through a variety of mechanisms, from its effects on the blood-brain barrier, the innate immune system, and synaptic function to the accumulation of amyloid-β (Aβ). Here, we discuss the role of apoE on the biophysical properties and metabolism of the Aβ peptide, the principal component of amyloid plaques and cerebral amyloid angiopathy (CAA). CAA is characterized by the deposition of amyloid proteins (including Aβ) in the leptomeningeal medium and small arteries, which is found in most AD cases but sometimes occurs as an independent entity. Accumulation of these pathologies in the brain is one of the pathological hallmarks of AD. Beyond Aβ, we will extend the discussion to the potential role of apoE on other amyloidogenic proteins found in AD, and also a number of diverse neurodegenerative diseases.
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“ApoE4 alters APP processing and Aβ degradation (reviewed in Benilova et al., 2012; Haass et al., 2012; Huynh et al., 2017; Lane-Donovan and Herz, 2017; Pohlkamp et al., 2017; Yamazaki et al., 2019)”
From NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load (2021) · cites this paper as Huynh et al., 2017
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“Results of co-immunostaining experiments showed increased levels of APOE, a well-known factor in Aβ aggregation40, in microglia (Fig. 4g) and amyloid plaques in Cnp−/−;5×FAD mice (Fig. 4h).”
From Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease (2023) · cites this paper as [40]
In the citing paper
“In AD, numerous studies have also shown that apoE functions as an important regulator of brain amyloid (amyloid β-peptide or Aβ) deposition and clearance (apoE2>E3>E4), which most likely accounts for one of the known mechanisms as to how APOE4 increase AD risk [30].”
From 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner (2020) · cites this paper as [30]
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Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
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Self-citationCerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways
Greenberg, S. M., Bacskai, B. J., Hernandez-Guillamon, M., Pruzin, J., Sperling, R., & van Veluw, S. J. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-019-0281-2 · Cited by 947
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Metadata
- Authors
- Huynh, T.-P. V., Davis, A. A., Ulrich, J. D., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Holtzman, David M.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 58
- Issue
- 5
- Pages
- 824-836
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC5408619
- OpenAlex
- W2591809865
- Cited by
- 210
- References
- 209
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 21 · 2023: 29 · 2022: 22 · 2021: 19 · 2020: 23 · 2019: 32 · 2018: 22 · 2017: 9
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-08-01)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (NS090934, AG047644)
- 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, Alzheimer's disease, amyloid-beta, cerebral amyloid angiopathy, amyloid plaques, amyloidogenic proteins, late-onset Alzheimer's disease, blood-brain barrier, innate immunity, synaptic function, amyloid-beta metabolism, neurodegenerative diseases
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Humans, Risk Factors, Amyloid beta-Peptides
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