Effect of Apolipoprotein E Allele ε4 on the Initial Phase of Amyloid β-Protein Accumulation in the Human Brain

Morishima-Kawashima, Maho; Oshima, Noriko; Ogata, Hiromitsu; Yamaguchi, Haruyasu; Yoshimura, Masahiro; Sugihara, Shiro; Ihara, Yasuo

doi:10.1016/s0002-9440(10)64847-x

Cited by 120Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Effect of Apolipoprotein E Allele ε4 on the Initial Phase of Amyloid β-Protein Accumulation in the Human Brain

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Morishima-Kawashima, Maho, Oshima, Noriko, Ogata, Hiromitsu, Yamaguchi, Haruyasu, Yoshimura, Masahiro, Sugihara, Shiro, Ihara, Yasuo·2000·The American Journal of Pathology

DOI 10.1016/s0002-9440(10)64847-xPMC PMC1885772

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Abstract

Deposition of amyloid ss-protein (Ass), a hallmark of Alzheimer's disease, occurs to some extent in the brains of most elderly individuals. We sought to learn when Ass deposition begins and how deposition is affected by apolipoprotein E allele epsilon4, a strong risk factor for late-onset Alzheimer's disease. Using an improved extraction protocol and specific enzyme-linked immunosorbent assay, we quantified the levels of Ass40 and Ass42 in the insoluble fractions of brains from 105 autopsy cases, aged 22 to 81 years at death, who showed no signs of dementia. Ass40 and Ass42 were detected in the insoluble fractions from all of the brains examined; low levels were even found in the brains of patients as young as 20 to 30 years of age. The incidence of significant Ass accumulation increased age-dependently, with Ass42 levels beginning to rise steeply in some patients in their late 40's, accompanied by much smaller increases in Ass40 levels. The presence of the apolipoprotein E epsilon4 allele was found to significantly enhance the accumulation of Ass42 and, to a lesser extent, that of Ass40. These findings strongly suggest that the presence of epsilon4 allele results in an earlier onset of Ass42 accumulation in the brain.

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Autopsy studies reveal at the time of death, brains from cognitively normal individuals frequently contain plaques.
“Autopsy studies reveal at the time of death, brains from cognitively normal individuals frequently contain plaques [77, 234-237].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [234]

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Authors: Morishima-Kawashima, M., Oshima, N., Ogata, H., Yamaguchi, H., Yoshimura, M., Sugihara, S., & Ihara, Y.
Affiliations: Japan Science and Technology Agency (JP)
National Institute of Public Health (JP)
Gunma University (JP)
Kyoto Prefectural University of Medicine (JP)
Gunma Prefectural Cancer Center (JP)
Corresponding author: Ihara, Yasuo
ORCID: Yoshimura, Masahiro
Ihara, Yasuo
Venue: The American Journal of Pathology
Publisher: Elsevier BV
Published: 2000-12
Volume: 157
Issue: 6
Pages: 2093-2099
ISSN: 0002-9440 (ISSN-L)
DOI: 10.1016/s0002-9440(10)64847-x
PMC: PMC1885772
OpenAlex: W2084025227
Cited by: 119
References: 40
Citations by year: 2026: 1 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 7
FWCI: 2.45
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: American Journal Of Pathology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
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: amyloid-beta, APOE ε4, Alzheimer's disease, amyloid deposition, age-dependent accumulation, genetic risk factors, brain aging
MeSH terms: Adult, Aged, Aged, 80 and over, Aging, Alleles, Alzheimer Disease, Apolipoproteins E, Brain, Cadaver, Female, Humans, Hydrochloric Acid, Male, Methods, Middle Aged, Solubility, Amyloid beta-Peptides, Guanidine, Apolipoprotein E4

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Effect of Apolipoprotein E Allele ε4 on the Initial Phase of Amyloid β-Protein Accumulation in the Human Brain

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