Aβ1–40 but not Aβ1–42 levels in cortex correlate with apolipoprotein E ϵ4 allele dosage in sporadic Alzheimer's disease
Abstract
Apolipoprotein E (ApoE) epsilon4 allele is established to be a risk factor for the development of late-onset Alzheimer's disease (AD) which is associated with increased frequency of senile plaques and extent of amyloid angiopathy. In a recent report, we demonstrated that ApoE epsilon4 dosage correlates with an increase in A beta1-40 but not A beta1-42/43-immunoreactive plaques. In the present study, we sought to confirm this relationship at a biochemical level by using a sensitive ELISA to measure the amounts of A beta1-42/43 and A beta1-40 in cerebral cortex in 36 cases of sporadic AD. We found that dosage of ApoE epsilon4 allele correlated significantly with cortical A beta1-40 levels, while levels of A beta1-42 showed no significant association with genotype. These results parallel our immunohistochemical findings and suggest that A beta1-40 may play a key role in the pathogenesis of late-onset sporadic AD.
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Several reports suggest that Aβ40 preferentially aggregates in an apoE4 gene dose-dependent manner in AD subjects.
“Interestingly, there have been several reports suggesting that Aβ40 preferentially aggregates in an apoE4 gene dose-dependent manner in AD subjects (Gearing et al., 1996; Ishii et al., 1997; Mann et al., 1997).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Ishii et al., 1997
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- Authors
- Ishii, K., Tamaoka, A., Mizusawa, H., Shoji, S.-I., Ohtake, T., Fraser, P. E., Takahashi, H., Tsuji, S., Gearing, M., Mizutani, T., Yamada, S., Kato, M., St.George-Hyslop, P. H., Mirra, S. S., & Mori, H.
- Affiliations
- University of Tsukuba (JP)
- Tokyo Metropolitan Neurological Hospital (JP)
- University of Toronto (CA)
- Brain Research Institute, Niigata University (JP)
- Emory University (US)
- Tokyo Metropolitan Institute of Gerontology (JP)
- Tokyo Institute of Psychiatry (JP)
- Corresponding author
- Mori, Hiroshi
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1997-02
- Volume
- 748
- Issue
- 1-2
- Pages
- 250-252
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2112357968
- Cited by
- 85
- References
- 5
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2022: 1 · 2021: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2013: 2 · 2012: 1
- FWCI
- 6.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Japan Society for the Promotion of Science
- National Institute on Aging (P30AG010130, AG-10130)
- Topics
- Health Sciences › Medicine › Physiology › 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
- Alzheimer's disease, APOE ε4, APOE genotype, Aβ40, amyloid-beta 42, cerebral cortex, sporadic Alzheimer's disease, late-onset Alzheimer's disease, amyloid plaques, pathogenesis
- MeSH terms
- Aged, Alleles, Alzheimer Disease, Apolipoproteins E, Cerebral Cortex, Humans, Middle Aged, Peptide Fragments, Amyloid beta-Peptides, Gene Dosage, Apolipoprotein E4
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