Cerebral amyloid angiopathy (CAA) often coexists with Alzheimer's disease (AD). APOE4 is a strong genetic risk factor for both AD and CAA. Sex-dependent differences have been shown in AD as well as in cerebrovascular diseases. Therefore, we examined the effects of APOE4, sex, and pathological components on CAA in AD subjects. A total of 428 autopsied brain samples from pathologically confirmed AD cases were analyzed. CAA severity was histologically scored in inferior parietal, middle frontal, motor, superior temporal and visual cortexes. In addition, subgroups with severe CAA (n = 60) or without CAA (n = 39) were subjected to biochemical analysis of amyloid-β (Aβ) and apolipoprotein E (apoE) by ELISA in the temporal cortex. After adjusting for age, Braak neurofibrillary tangle stage and Thal amyloid phase, we found that overall CAA scores were higher in males than females. Furthermore, carrying one or more APOE4 alleles was associated with higher overall CAA scores. Biochemical analysis revealed that the levels of detergent-soluble and detergent-insoluble Aβ40, and insoluble apoE were significantly elevated in individuals with severe CAA or APOE4. The ratio of Aβ40/Aβ42 in insoluble fractions was also increased in the presence of CAA or APOE4, although it was negatively associated with male sex. Levels of insoluble Aβ40 were positively associated with those of insoluble apoE, which were strongly influenced by CAA status. Pertaining to insoluble Aβ42, the levels of apoE correlated regardless of CAA status. Our results indicate that sex and APOE genotypes differentially influence the presence and severity of CAA in AD, likely by affecting interaction and aggregation of Aβ40 and apoE.

中文翻译：

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性别和APOE4对阿尔茨海默氏病脑淀粉样血管病的影响。

脑淀粉样血管病（CAA）通常与阿尔茨海默氏病（AD）共存。APOE4是AD和CAA的强大遗传风险因素。在AD以及脑血管疾病中已经显示出性别依赖性差异。因此，我们检查了APOE4，性别和病理成分对AD受试者CAA的影响。总共428份经病理证实的AD病例的尸体脑样本进行了分析。从组织学上对下顶，中额叶，运动，颞上皮和视觉皮层进行CAA严重程度评分。此外，对具有严重CAA的亚组（n = 60）或没有CAA的亚组（n = 39）进行颞叶皮层中ELISA的淀粉样β（Aβ）和载脂蛋白E（apoE）的生化分析。在调整了年龄，Braak神经原纤维缠结阶段和Thal淀粉样蛋白阶段之后，我们发现，男性的总体CAA得分高于女性。此外，携带一个或多个APOE4等位基因与更高的总体CAA得分相关。生化分析表明，患有严重CAA或APOE4的个体的去污剂可溶和去污剂不溶性Aβ40和不溶性apoE的水平显着升高。在存在CAA或APOE4的情况下，不溶性组分中Aβ40/Aβ42的比例也增加，尽管与男性性别呈负相关。不溶性Aβ40的水平与不溶性apoE的水平呈正相关，这受CAA状态的强烈影响。与不溶性Aβ42有关，apoE的水平相关，而与CAA状态无关。我们的结果表明，性别和APOE基因型对AD中CAA的存在和严重程度有不同的影响，