Apolipoprotein E and Dementia in Parkinson Disease: A Meta-analysis
Abstract
Objective To understand the relationship of apolipoprotein E (APOE) polymorphism to dementia in Parkinson disease (PD) because the APOE epsilon4 allele is linked to Alzheimer disease. Data source We reviewed MEDLINE, BIOSIS Previews, and ISI Web of Science from January 1, 1966, to May 7, 2004, supplemented by citation analysis from retrieved articles. Study selection Case-control studies using clinical or pathologic criteria for PD and dementia, and with complete APOE genotype frequencies data. Data extraction We compared estimated prevalence odds ratios for dementia in PD in relation to each allele. We also looked for evidence of heterogeneity and publication bias and performed a stratified analysis on several study characteristics. Data synthesis Data analyses suggest publication bias and heterogeneity of source data for the epsilon4 allele (homogeneity P = .2; Begg and Mazumdar, P = .06; and Egger et al, P = .1). The estimated odds ratios for development of dementia in PD are 1.6 for epsilon4 (95% confidence interval, 1.0-2.5); 1.3 for epsilon2 (95% confidence interval, 0.73-2.4); and 0.54 for epsilon3 (95% confidence interval, 0.18-1.6). The odds ratio estimates for epsilon4 were higher for studies published in 1996 or later (2.3 vs 1.0) and for studies conducted outside North American sites (2.4 vs 1.2). Conclusions The APOE epsilon4 allele appears to be associated with a higher prevalence of dementia in PD. Publication bias and heterogeneous source data may, however, co…
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The other mechanisms of APOE4 dysfunction probably explain the association with neurodegenerative diseases in general, such as Parkinson's disease, Lewy body dementia, TDP-43 proteinopathy, and vascular dementia.
“The other mechanisms of APOE4 dysfunction probably explain the association with neurodegenerative diseases in general, such as Parkinson’s disease (odds ratio ~1.6–4.19) and Lewy body dementia (odds ratio ~2.4–6.1) (Bras et al, 2014; Guerreiro et al, 2018; Huang et al, 2006; Irwin et al, 2012; Tropea et al, 2018; Tsuang et al, 2013); TDP-43 proteinopathy (odds ratio ~2) (Josephs et al, 2014; Wenn”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Huang et al, 2006
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Bias in meta-analysis detected by a simple, graphical
Stuck, A. E., Rubenstein, L. Z., Wieland, D., Vandenbroucke, J. P., Irwig, L., Macaskill, P., Berry, G., Glasziou, P., Seagroatt, V., Stratton, I., et al. (1998) · BMJ · doi:10.1136/bmj.316.7129.469 · Cited by 699 · see citing works
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Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425 · see citing works
α-Synuclein in Cerebrospinal Fluid of Alzheimer's Disease and Mild Cognitive Impairment
Korff, A., Liu, C., Ginghina, C., Shi, M., Zhang, J., & Initiative, F. T. A. D. N. (2013) · Journal of Alzheimer’s Disease · doi:10.3233/jad-130458 · Cited by 95 · see citing works
Preman, P., Moechars, D., Fertan, E., Wolfs, L., Serneels, L., Shah, D., Lamote, J., Poovathingal, S., Snellinx, A., Mancuso, R., et al. (2024) · EMBO Molecular Medicine · doi:10.1038/s44321-024-00162-7 · Cited by 32 · see citing works
- Authors
- Huang, X., Chen, P., Kaufer, D. I., Tröster, A. I., & Poole, C.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2006-02-01
- Volume
- 63
- Issue
- 2
- Pages
- 189
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W162979156
- Cited by
- 128
- References
- 1
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 8 · 2017: 6 · 2016: 9 · 2015: 6 · 2014: 5 · 2013: 6 · 2012: 8
- FWCI
- 5.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (K23AG021491, AG21491)
- National Institute of Environmental Health Sciences (ES 10126, P30ES010126)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- apolipoprotein E, APOE polymorphism, Parkinson's disease, dementia, APOE ε4, APOE ε2 allele, APOE ε3 allele, genetic risk factors, publication bias
- MeSH terms
- Apolipoproteins E, Dementia, Genotype, Humans, Parkinson Disease, Odds Ratio, Case-Control Studies, Genetic Predisposition to Disease
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