The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged
Silvia Ingala1, Linda Mazzai2, Carole H Sudre3
1Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Abstract:
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.
Insights
The APOE-ε4 genotype is linked to more cerebral microbleeds (CMBs) in older adults, particularly in lobar areas. This suggests increased cerebral vessel fragility in APOE-ε4 homozygotes, potentially indicating heightened vascular vulnerability.
Area of Science:
- Neuroimaging
- Genetics
- Vascular Neurology
Background:
- Cerebral microbleeds (CMBs) are associated with APOE-ε4 genotype in Alzheimer's disease, but findings are inconsistent.
- Investigating APOE genotype effects on CMBs in cognitively unimpaired individuals is crucial for understanding early vascular changes.
Purpose of the Study:
- To examine the association between APOE genotype and CMBs in a cohort of middle- and old-aged cognitively unimpaired individuals.
- To determine if APOE-ε4 dose influences CMB prevalence and characteristics.
Main Methods:
- Analysis of magnetic resonance scans from 564 participants in the ALFA cohort.
- Quantitative MRI including visual CMB ratings, atrophy measures, and white matter hyperintensity (WMH) segmentation.
- Comparison of CMB prevalence and number across APOE genotype groups (ε4 homozygotes, heterozygotes, non-carriers, and ε2 carriers).
Main Results:
- CMB prevalence was 17% and increased with age.
- A trend for increased CMBs with higher APOE-ε4 dose was observed.
- APOE-ε4 homozygotes had significantly more CMBs than heterozygotes and non-carriers, driven by lobar CMBs.
- CMBs co-localized with white matter hyperintensities (WMH).
Conclusions:
- The APOE-ε4 genotype, particularly homozygosity, is associated with increased cerebral microbleeds, especially in lobar locations.
- These findings suggest greater cerebral vessel fragility in APOE-ε4 homozygous individuals.
- The co-occurrence of CMBs and WMH indicates shared vascular vulnerability in specific brain regions.
