TY - JOUR
T1 - The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals
AU - ALFA Study
AU - Ingala, Silvia
AU - Mazzai, Linda
AU - Sudre, Carole H.
AU - Salvadó, Gemma
AU - Brugulat-Serrat, Anna
AU - Wottschel, Viktor
AU - Falcon, Carles
AU - Operto, Grégory
AU - Tijms, Betty
AU - Gispert, Juan Domingo
AU - Molinuevo, José Luis
AU - Barkhof, Frederik
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - APOE
KW - Alzheimer's disease (AD)
KW - Cerebral microbleeds (CMBs)
KW - Magnetic resonance imaging (MRI)
KW - White matter hyperintensities (WMH)
UR - http://www.scopus.com/inward/record.url?scp=85089181883&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.neurobiolaging.2020.06.015
DO - https://doi.org/10.1016/j.neurobiolaging.2020.06.015
M3 - Article
C2 - 32791423
SN - 0197-4580
VL - 95
SP - 104
EP - 114
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -