Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Theranostics. 2020 Aug 21;10(23):10563-10572. doi: 10.7150/thno.48522. eCollection 2020.
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 F-AV-1451 positron emission tomography (PET) and magnetic resonance imaging (MRI). Preprocessed F-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. F-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. Female APOE ε4 carriers (FACs) had significant higher F-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 F-AV-1451 SUVRs and lower gray matter volume between FACs compared to the NFACs. Negative correlations between ROI F-AV-1451 SUVRs and gray matter volumes were significant after adjusting for age and years of education. 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 F-AV-1451 PET and structural MRI.
本研究旨在使用定量 F-AV-1451 正电子发射断层扫描 (PET) 和磁共振成像 (MRI) 评估性别和载脂蛋白 E (APOE) ε4 等位基因与老年阿尔茨海默病 (AD) 患者脑 tau 沉积和萎缩的相关性。 从阿尔茨海默病神经影像学倡议 (ADNI) 数据库下载了 57 名老年 AD 患者的 F-AV-1451 tau PET 预处理、原始 T1 加权结构 MRI 图像、人口统计学信息、脑脊液 (CSF) 总 tau (t-tau) 和磷酸化 tau (p-tau) 测量值。 对所有预处理的 PET 图像应用迭代再模糊化的范西特局部体积校正 (PVC) 方法。 MRI 图像用于 PET 空间归一化和灰质体积计算。F-AV-1451 PET 标准化摄取值比 (SUVR) 相对于小脑灰质进行计算。在 ROI 和体素水平评估性别和 APOE ε4 状态对 SUVR 和灰质体积的影响。 与非 APOE ε4 携带者 (NFACs) 相比，女性 APOE ε4 携带者 (FACs) 在外侧颞叶、顶叶、后扣带回、内侧颞叶、颞下回、内嗅皮层、杏仁核和海马旁回区域的 F-AV-1451 SUVR 显著升高，后扣带回、内侧颞叶、颞下回和杏仁核区域的灰质体积减小。与非 FACs（女性 APOE ε4 非携带者、男性 APOE ε4 携带者和男性 APOE ε4 非携带者）相比，体素分析显示，与 NFACs 相比，FACs 的额前脑和边缘簇中 F-AV-1451 SUVR 更高，灰质体积更低。 在调整年龄和受教育年限后，ROI F-AV-1451 SUVR 与灰质体积之间的负相关具有统计学意义。 在老年 AD 患者中，性别改变了 APOE ε4 等位基因对特定脑区 tau 沉积和灰质体积的影响。FACs 的脑区特异性 tau PET SUVR 升高，灰质体积减少与 NFACs 相比。 该研究为使用 F-AV-1451 PET 和结构 MRI 进行 AD 诊断和治疗评估的精准医学提供了依据。
