The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals
The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals
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DOI：
10.1016/j.neurobiolaging.2020.06.015
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发表时间：
2020-11-01
影响因子：
4.2
通讯作者：
Barkhof, Frederik
中科院分区：
文献类型：
--
作者：
Ingala, Silvia;Mazzai, Linda;Barkhof, Frederik
在阿尔茨海默病中，脑微出血（CMB）和载脂蛋白E基因型之间的正相关性已被报道，但显示出相互矛盾的结果。我们研究了APOE基因型对认知功能未受损的中老年人群中CMB的影响。纳入了来自ALFA（阿尔茨海默病和家族）队列的参与者，并评估了他们的磁共振扫描（n = 564，50% APOE-β 4携带者）。定量磁共振分析包括视觉评分、萎缩测量和白色高信号（WMH）分割。CMB的患病率为17%，随年龄增加而增加（p < 0.05），并遵循与APOE-β 4剂量平行的增加趋势。与杂合子和非携带者相比，APOE-epsilon 4纯合子中的CMB数量显着较高（p < 0.05）。这种关联是由肺叶CMB驱动的（p < 0.05）。CMB与WMH共定位（p < 0.05）。未发现CMB与APOE-104 2、灰质体积和认知能力之间的相关性。我们的结果表明，APOE-104纯合子的脑血管更脆弱，尤其是在脑叶部位。CMB和WMH的共同发生表明这种变化定位于血管脆弱性增加的区域。(C)2020作者爱思唯尔公司出版
Positive associations between cerebral microbleeds (CMBs) and APOE-epsilon 4 (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-epsilon 4 genotype. Participants from ALFA (Alzheimer and Families) cohort were included and their magnetic resonance scans assessed (n = 564, 50% APOE-epsilon 4 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-epsilon 4 dose. The number of CMBs was significantly higher in APOE-epsilon 4 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-epsilon 2, gray matter volumes, and cognitive performance were found. Our results suggest that cerebral vessels of APOE-epsilon 4 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. (C) 2020 The Authors. Published by Elsevier Inc.