The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals
Open accessAbstract
Positive associations between cerebral microbleeds (CMBs) and APOE-ε4 (apolipoprotein E) genotype have been reported in Alzheimer's disease, but show conflicting results. We investigated the effect of APOE genotype on CMBs in a cohort of cognitively unimpaired middle- and old-aged individuals enriched for APOE-ε4 genotype. Participants from ALFA (Alzheimer and Families) cohort were included and their magnetic resonance scans assessed (n = 564, 50% APOE-ε4 carriers). Quantitative magnetic resonance analyses included visual ratings, atrophy measures, and white matter hyperintensity (WMH) segmentations. The prevalence of CMBs was 17%, increased with age (p < 0.05), and followed an increasing trend paralleling APOE-ε4 dose. The number of CMBs was significantly higher in APOE-ε4 homozygotes compared to heterozygotes and non-carriers (p < 0.05). This association was driven by lobar CMBs (p < 0.05). CMBs co-localized with WMH (p < 0.05). No associations between CMBs and APOE-ε2, gray matter volumes, and cognitive performance were found. Our results suggest that cerebral vessels of APOE-ε4 homozygous are more fragile, especially in lobar locations. Co-occurrence of CMBs and WMH suggests that such changes localize in areas with increased vascular vulnerability.
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Studies in younger and presymptomatic individuals showed cerebral microbleeds are significantly higher in number in APOE ε4 carriers.
“Studies in younger and presymptomatic individuals showed that cerebral microbleeds are significantly higher in number in APOE ε4 carriers [40].”
From The use of neuroimaging techniques in the early and differential diagnosis of dementia (2023) · cites this paper as [40]
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The use of neuroimaging techniques in the early and differential diagnosis of dementia
Chouliaras, L., & O’Brien, J. T. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02215-8 · Cited by 186 · see citing works
“Studies in younger and presymptomatic individuals showed that cerebral microbleeds are signi fi cantly higher in number in APOE ε 4 carriers [40].”
Background
- Authors
- Ingala, S., Mazzai, L., Sudre, C. H., Salvadó, G., Brugulat-Serrat, A., Wottschel, V., Falcon, C., Operto, G., Tijms, B., Gispert, J. D., Molinuevo, J. L., & Barkhof, F.
- Affiliations
- Amsterdam Neuroscience (NL)
- University of Padua (IT)
- King's College London (GB)
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Universitat Pompeu Fabra (ES)
- Corresponding author
- Ingala, Silvia
- Gispert, Juan Domingo
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 95
- Pages
- 104-114
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W3038537724
- Cited by
- 25
- References
- 10
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 3 · 2021: 3 · 2020: 1
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Aging (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- EU
- EFPIA, Belgium
- Dementia Consortium, United Kingdom
- Alzheimer’s Society
- NIHR
- UCLH, United Kingdom
- Topics
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- cerebral microbleeds, APOE ε4, APOE genotype, white matter hyperintensities, lobar microbleeds, cognitive impairment, middle-aged and older adults, Alzheimer's disease risk, cerebral small vessel disease
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Cerebral Hemorrhage, Cognition, Female, Genotype, Homozygote, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Genetic Association Studies, White Matter
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