Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Chemistry, University of Southern Indiana, Evansville, Indiana, USA.
Alzheimers Dement. 2023 Nov;19 Suppl 9(Suppl 9):S49-S63. doi: 10.1002/alz.13403. Epub 2023 Jul 26.
We used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early-onset Alzheimer's disease (EOAD).
We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non-Alzheimer's disease (EOnonAD) participants from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification. Voxel-wise multiple linear regressions yielded statistical brain maps of gray matter density, amyloid, and tau PET burden.
EOAD females had greater amyloid and tau PET burdens than males. EOAD female APOE ε4 non-carriers had greater amyloid PET burdens and greater gray matter atrophy than female ε4 carriers. EOnonAD female ε4 non-carriers also had greater gray matter atrophy than female ε4 carriers.
The effects of sex and APOE ε4 must be considered when studying these populations.
Novel analysis examining the effects of biological sex and apolipoprotein E ε4 (APOE ε4) carrier status on neuroimaging biomarkers among early-onset Alzheimer's disease (EOAD), early-onset non-AD (EOnonAD), and cognitively normal (CN) participants. Female sex is associated with greater pathology burden in the EOAD cohort compared to male sex. The effect of APOE ε4 carrier status on pathology burden was the most impactful in females across all cohorts.
我们使用性别和载脂蛋白 E ε4（APOE ε4）携带状态作为预测早发性阿尔茨海默病（EOAD）病理性负担的指标。
我们纳入了来自纵向早发性阿尔茨海默病研究（LEADS）的 77 名认知正常（CN）、230 名 EOAD 和 70 名 EO 非阿尔茨海默病（EOnonAD）参与者的基线数据。我们按男性和女性对每个诊断组进行分层，然后按 APOE ε4 携带状态进一步细分每个性别，并比较每个分层中的影像学生物标志物。体素-wise 多元线性回归生成了灰质密度、淀粉样蛋白和 tau PET 负荷的统计脑图。
EOAD 女性的淀粉样蛋白和 tau PET 负荷均大于男性。EOAD 女性 APOE ε4 非携带者的淀粉样蛋白 PET 负荷和灰质萎缩程度大于女性 ε4 携带者。EOnonAD 女性 APOE ε4 非携带者的灰质萎缩程度也大于女性 ε4 携带者。
在研究这些人群时，必须考虑性别和 APOE ε4 的影响。
这项新的分析研究了生物学性别和载脂蛋白 E ε4（APOE ε4）携带状态对早发性阿尔茨海默病（EOAD）、早发性非 AD（EOnonAD）和认知正常（CN）参与者神经影像学生物标志物的影响。与男性相比，女性的 EOAD 队列中存在更大的病理学负担。在所有队列中，APOE ε4 携带状态对病理学负担的影响在女性中最为显著。
