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Apolipoprotein E ε4 allele, AD pathology, and the clinical expression of Alzheimer’s disease
Abstract
Objective To test the hypothesis that the APOE epsilon4 allele is associated with the clinical manifestations of AD through an association with the pathologic hallmarks of disease. Methods Participants were older Catholic nuns, priests, and brothers who agreed to annual neurologic and neuropsychological evaluation for AD and other common neurologic conditions and brain autopsy at the time of death. There were 77 persons without dementia and 51 with probable AD; 38 participants had one or more epsilon4 alleles. Results In logistic regression analyses, controlling for age, sex, and education, the epsilon4 allele was strongly associated with the likelihood of clinical AD (odds = 3.46, 95% CI = 1.44 to 8.33). However, controlling for the effect of AD pathology, the association of the epsilon allele with clinical AD was reduced by >50% and was no longer significant (odds = 1.58, 95% CI = 0.56 to 4.43). Similarly, in linear regression analyses, controlling for age, sex, and education, the epsilon4 allele was strongly associated with level of cognitive function proximate to death (regression coefficient = -0.477, p = 0.005). However, after controlling for the effect of AD pathology, the association of the epsilon4 allele with level of cognition was reduced by >80% and was no longer significant (regression coefficient = -0.093). Similar results were found in analyses using separate measures of neuritic plaques, diffuse plaques, and neurofibrillary tangles, and in analyses of five dif…
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“In our previous study, we found that the inter-rater reliability of the counts of AD pathologic indices were from 0.89 to 0.93, supporting reproducibility of these measures [13].”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [13]
In the citing paper
“In our previous study, we showed that the regional standardized scores were highly correlated with the global AD pathology score (r range: 0.47–0.73, median r = 0.67) and the Chronbach α coefficient was 0.90, indicating high internal consistency and supporting use of the global AD pathology score [13].”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [13]
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Metadata
- Authors
- Bennett, D. A., Wilson, R. S., Schneider, J. A., Evans, D. A., Aggarwal, N. T., Arnold, S. E., Cochran, E. J., Berry-Kravis, E., & Bienias, J. L.
- Affiliations
- From the Rush Alzheimer’s Disease Center and Rush Institute for Healthy Aging (Drs. Bennett, Wilson, Schneider, Evans, Aggarwal, and Bienias); Department of Neurological Sciences (Drs. Bennett, Wilson, Schneider, Evans, Aggarwal, Cochran, and Berry-Kravis); Department of Psychology (Dr. Wilson); Department of Pathology (Drs. Schneider and Cochran); Department of Internal Medicine (Drs. Evans and Bienias), Department of Pediatrics (Dr. Berry-Kravis), Rush Presbyterian-St. Luke’s Medical Center,...
- Venue
- Neurology
- Published
- 2003-01-28
- Volume
- 60
- Issue
- 2
- Pages
- 246-252
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2005578478
- Cited by
- 282
- References
- 64
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 11 · 2023: 10 · 2022: 9 · 2021: 15 · 2020: 9 · 2019: 11 · 2018: 10 · 2017: 13 · 2016: 10 · 2015: 10 · 2014: 8 · 2013: 9 · 2012: 15
- FWCI
- 12.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-15819, AG 10161, P30AG010161)
- 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
- APOE ε4, Alzheimer's disease, neuropathology, neuritic plaques, neurofibrillary tangles, cognitive function, episodic memory, semantic memory, working memory, perceptual speed, visuospatial ability, women religious, brain autopsy
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Brain, Cognition Disorders, Educational Status, Female, Humans, Longitudinal Studies, Male, Memory Disorders, Neuropsychological Tests, Risk Factors, Linear Models, Logistic Models, Odds Ratio, Disease Progression, Genetic Predisposition to Disease, Apolipoprotein E4
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