Effects of APOE ‐ε4 allele load on brain morphology in a cohort of middle‐aged healthy individuals with enriched genetic risk for Alzheimer's disease
Open accessAbstract
Introduction: Apolipoprotein E ( APOE )‐ε4 is the major genetic risk factor for Alzheimer's disease. However, the dose‐dependent impact of this allele on brain morphology of healthy individuals remains unclear. Methods: We analyzed gray matter volumes (GMvs) in a sample of 533 healthy middle‐aged individuals with a substantial representation of ε4‐carriers (207 heterozygotes and 65 homozygotes). Results: We found APOE ‐ε4 additive GMv reductions in the right hippocampus, caudate, precentral gyrus, and cerebellar crus. In these regions, the APOE genotype interacted with age, with homozygotes displaying lower GMv after the fifth decade of life. APOE ‐ε4 was also associated to greater GMv in the right thalamus, left occipital gyrus, and right frontal cortex. Discussion: Our data indicate that APOE ‐ε4 exerts additive effects on GMv in regions relevant for Alzheimer's disease pathophysiology already in healthy individuals. These findings elucidate the mechanisms underlying the increased Alzheimer's disease risk in ε4‐carriers, suggesting a dose‐dependent disease vulnerability on the brain structure level.
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Increased thalamic volume and hypermetabolism with amyloid pathology have been reported among APOE4 carriers.
“The role of thalamic structure and function in AD appears complex and perhaps nonlinear, as thalamic atrophy in MCI [48] and hypometabolism in APOE4 carriers [49] have been observed, whereas others have reported increased thalamic volume [50] and hypermetabolism with amyloid pathology [51] among APOE4 carriers.”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [50]
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References 57 · Cited by 124
- Authors
- Cacciaglia, R., Molinuevo, J. L., Falcón, C., Brugulat‐Serrat, A., Sánchez‐Benavides, G., Gramunt, N., Esteller, M., Morán, S., Minguillón, C., Fauria, K., Gispert, J. D., & study, F. T. A.
- Affiliations
- Pasqual Maragall Foundation (ES)
- Barcelonabeta Brain Research Center Pasqual Maragall Foundation Barcelona Catalonia Spain
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Corresponding author
- Gispert, Juan Domingo
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2018-03-28
- Volume
- 14
- Issue
- 7
- Pages
- 902-912
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2795068887
- Cited by
- 124
- References
- 57
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 14 · 2023: 17 · 2022: 14 · 2021: 23 · 2020: 22 · 2019: 14 · 2018: 7 · 2017: 1
- FWCI
- 12.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by-nc-nd)
- Funders
- “la Caixa” Foundation (PI12/00326)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- APOE ε4, apolipoprotein E
- MeSH terms
- Aged, Aging, Alleles, Alzheimer Disease, Cerebral Cortex, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Risk Factors, Cohort Studies, Apolipoprotein E4, Healthy Volunteers, Gray Matter
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