Alzheimer's disease (AD) is characterised by severe cognitive decline and pathological changes in the brain (brain atrophy, hyperphosphorylation of tau, and deposition of toxic amyloid-beta protein). Females have greater neuropathology (AD biomarkers and brain atrophy rates) and cognitive decline than males, however these effects can depend on diagnosis (amnestic mild cognitive impairment (aMCI) or AD) and APOE genotype (presence of ϵ4 alleles). Using the ADNI database (N=630 females, N=830 males), we analysed the effect of sex, APOE genotype (non-carriers or carriers of APOEϵ4 alleles), and diagnosis (cognitively normal (CN), early aMCI (EMCI), late aMCI (LMCI), probable AD) on cognition (memory and executive function), hippocampal volume, and AD biomarkers (CSF levels of amyloid beta, tau and ptau). Regardless of APOE genotype, memory scores were higher in CN, EMCI, and LMCI females compared to males but this sex difference was absent in probable AD, which may suggest a delay in the onset of cognitive decline or diagnosis and/or a faster trajectory of cognitive decline in females. We found that, regardless of diagnosis, CSF tau-pathology was disproportionately elevated in female carriers of APOEϵ4 alleles compared to males. In contrast, male carriers of APOEϵ4 alleles had reduced levels of CSF amyloid beta compared to females, irrespective of diagnosis. We also detected sex differences in hippocampal volume but the direction was dependent on the method of correction. Altogether results suggest that across diagnosis females show greater memory decline compared to males and APOE genotype affects AD neuropathology differently in males and females which may influence sex differences in incidence and progression of aMCI and AD.

中文翻译：

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性别会影响APOE基因型和阿尔茨海默氏病对神经病理学和记忆的诊断

阿尔茨海默氏病（AD）的特征是大脑严重的认知能力下降和病理变化（脑萎缩，tau过度磷酸化和有毒的淀粉样β蛋白沉积）。女性比男性具有更大的神经病理学（AD生物标志物和脑萎缩率）和认知能力下降，但是这些影响可能取决于诊断（轻度遗忘性认知障碍（aMCI）或AD）和APOE基因型（存在ϵ4等位基因）。使用ADNI数据库（N = 630女性，N = 830男性），我们分析了性别，APOE基因型（非携带者或APOEϵ4等位基因携带者）和诊断（认知正常（CN），早期aMCI（EMCI））的影响，晚期aMCI（LMCI），可能的AD（认知能力（记忆和执行功能），海马体积和AD生物标志物（CSF的淀粉样β，tau和ptau））。不论APOE基因型如何，CN，EMCI和LMCI女性的记忆评分高于男性，但可能的AD中没有这种性别差异，这可能暗示女性认知能力下降或诊断的延迟和/或认知能力下降的轨迹更快。我们发现，无论诊断如何，与男性相比，APOEϵ4等位基因的女性携带者的CSF tau病理学均不成比例地升高。相反，与女性无关，APOEϵ4等位基因的男性携带者与女性相比，CSF淀粉样蛋白β水平降低。我们还检测了海马体积的性别差异，但方向取决于矫正方法。