The objective of this study was to assess the association of sex and the apolipoprotein E (APOE) ε4 allele with brain tau deposition and atrophy in older adults with Alzheimer's disease (AD) using quantitative ¹⁸F-AV-1451 positron emission tomography (PET) and magnetic resonance imaging (MRI)./nMethods: Preprocessed ¹⁸F-AV-1451 tau PET, raw T1-weighted structural MR images, demographic information, cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) measurements from 57 elderly individuals with AD were downloaded from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. An iteratively reblurred Van Cittert partial volume correction (PVC) method was applied to all preprocessed PET images. MRI images were used for PET spatial normalization and gray matter volume calculation. ¹⁸F-AV-1451 PET standardized uptake value ratio (SUVR) was calculated relative to the cerebellum gray matter. The effect of sex and APOE ε4 status on SUVR and gray matter volume were assessed at both region of interest (ROI) and voxelwise levels./nResults: Female APOE ε4 carriers (FACs) had significant higher ¹⁸F-AV-1451 SUVRs in the lateral temporal, parietal, posterior cingulate, medial temporal, inferior temporal, entorhinal cortex, amygdala and parahippocampal gyrus regions, and exhibited smaller gray matter volumes in the posterior cingulate, medial temporal, inferior temporal and amygdala regions, as compared to the non-FACs (NFACs) comprised of female APOE ε4 non-carriers, male APOE ε4 carriers and male APOE ε4 non-carriers. Voxelwise analysis revealed forebrain and limbic clusters with greater ¹⁸F-AV-1451 SUVRs and lower gray matter volume between FACs compared to the NFACs. Negative correlations between ROI ¹⁸F-AV-1451 SUVRs and gray matter volumes were significant after adjusting for age and years of education./nConclusions: Among elderly individuals with AD, sex modified the effects of the APOE ε4 allele on region-specific tau deposition and gray matter volume. FACs had elevated brain region-specific tau PET SUVR and decreased gray matter volume in comparison to NFACs. The study provides a basis for the use of precision medicine in the diagnosis of AD and evaluation of therapeutics using ¹⁸F-AV-1451 PET and structural MRI.

中文翻译：

---

性别和 APOE ε4 与患有阿尔茨海默病的老年人脑 tau 沉积和萎缩的关系。


本研究的目的是使用定量¹⁸ F-AV-1451 正电子发射断层扫描 (PET) 评估性别和载脂蛋白 E (APOE) ε4 等位基因与患有阿尔茨海默病 (AD) 的老年人脑 tau 沉积和萎缩的关系和磁共振成像 (MRI)。/n方法：预处理¹⁸ F-AV-1451 tau PET、原始 T1 加权结构 MR 图像、人口统计信息、脑脊液 (CSF) 总 tau (t-tau) 和磷酸化 tau (p -tau）从阿尔茨海默病神经影像倡议（ADNI）数据库下载了 57 名患有 AD 的老年患者的测量结果。对所有预处理的 PET 图像应用迭代再模糊 Van Cittert 部分体积校正 (PVC) 方法。 MRI 图像用于 PET 空间归一化和灰质体积计算。 ¹⁸ F-AV-1451 PET 标准化摄取值比 (SUVR) 是相对于小脑灰质计算的。在感兴趣区域 (ROI) 和体素水平上评估性别和 APOE ε4 状态对 SUVR 和灰质体积的影响。/n结果：女性 APOE ε4 携带者 (FAC) 的¹⁸ F-AV-1451 SUVR 显着更高与非对照组相比，外侧颞叶、顶叶、后扣带回、内侧颞叶、下颞叶、内嗅皮层、杏仁核和海马旁回区域的灰质体积较小。 FAC (NFAC) 由女性 APOE ε4 非携带者、男性 APOE ε4 携带者和男性 APOE ε4 非携带者组成。 体素分析显示，与 NFAC 相比，FAC 之间的前脑和边缘簇具有更多的^{18 个}F-AV-1451 SUVR，并且灰质体积更低。调整年龄和受教育年限后，ROI ¹⁸ F-AV-1451 SUVR 与灰质体积之间呈显着负相关。/n 结论：在患有 AD 的老年个体中，性别改变了 APOE ε4 等位基因对区域特异性 tau 的影响沉积和灰质体积。与 NFAC 相比，FAC 的大脑区域特异性 tau PET SUVR 升高，灰质体积减少。该研究为精准医学在 AD 诊断和使用¹⁸ F-AV-1451 PET 和结构 MRI 的治疗评估中的应用提供了基础。