性别介导了区域 tau 病理学与认知衰退之间的关系。
Sex Mediates Relationships Between Regional Tau Pathology and Cognitive Decline.
机构信息
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Brigham and Women's Hospital, Department of Neurology, Center for Alzheimer Research and Treatment, Boston, MA, USA.
出版信息
Ann Neurol. 2020 Nov;88(5):921-932. doi: 10.1002/ana.25878. Epub 2020 Aug 31.
OBJECTIVE
The goal of this study was to examine sex differences in tau distribution across the brain of older adults, using positron emission tomography (PET), and investigate how these differences might associate with cognitive trajectories.
METHODS
Participants were 343 clinically normal individuals (women, 58%; 73.8 [8.5] years) and 55 individuals with mild cognitive impairment (MCI; women, 38%; 76.9 [7.3] years) from the Harvard Aging Brain Study and the Alzheimer's Disease Neuroimaging Initiative. We examined F-Flortaucipir (FTP)-positron emission tomography (PET) signal across 41 cortical and subcortical regions of interest (ROIs). Linear regression models estimated the effect of sex on FTP-signal for each ROI after adjusting for age and cohort. We also examined interactions between sexAβ-PET positive / negative (+ / -) and sexapolipoprotein ε4 (APOEε4) status. Linear mixed models estimated the moderating effect of sex on the relationship between a composite of sex-differentiated tau ROIs and cognitive decline.
RESULTS
Women showed significantly higher FTP-signals than men across multiple regions of the cortical mantle (p < 0.007). β-amyloid (Aβ)-moderated sex differences in tau signal were localized to medial and inferio-lateral temporal regions (p < 0.007); Aβ + women exhibited greater FTP-signal than other groups. APOEε4-moderated sex differences in FTP-signal were only found in the lateral occipital lobe. Women with higher FTP-signals in composite ROI exhibited faster cognitive decline than men (p = 0.04).
INTERPRETATION
Tau vulnerability in women is not just limited to the medial temporal lobe and significantly contributed to greater risk of faster cognitive decline. Interactive effects of sex and Aβ were predominantly localized in the temporal lobe, however, sex differences in extra-temporal tau highlights the possibility of accelerated tau proliferation in women with the onset of clinical symptomatology. ANN NEUROL 2020;88:921-932.
目的
本研究旨在使用正电子发射断层扫描（PET）研究老年人大脑中tau 的分布是否存在性别差异，并探讨这些差异如何与认知轨迹相关联。
方法
参与者包括来自哈佛老化大脑研究（Harvard Aging Brain Study）和阿尔茨海默病神经影像学倡议（Alzheimer's Disease Neuroimaging Initiative）的 343 名临床正常个体（女性占 58%，年龄为 73.8 [8.5]岁）和 55 名轻度认知障碍（MCI）个体（女性占 38%，年龄为 76.9 [7.3]岁）。我们检查了 41 个皮质和皮质下感兴趣区域（ROI）的 F-Flortaucipir（FTP）-正电子发射断层扫描（PET）信号。在调整年龄和队列后，线性回归模型估计了性别对每个 ROI 的 FTP 信号的影响。我们还检查了性别Aβ-PET 阳性/阴性（+/-）和性别载脂蛋白 E4（APOEε4）状态之间的相互作用。线性混合模型估计了性别对性别差异tau ROI 与认知下降之间关系的调节作用。
结果
女性在皮质盖的多个区域的 FTP 信号明显高于男性（p < 0.007）。β-淀粉样蛋白（Aβ）调节 tau 信号的性别差异局限于内侧和下外侧颞区（p < 0.007）；Aβ+女性的 FTP 信号大于其他组。仅在外侧枕叶发现 APOEε4 调节的 FTP 信号性别差异。复合 ROI 中 FTP 信号较高的女性认知下降速度比男性快（p = 0.04）。
结论
女性的 tau 易感性不仅局限于内侧颞叶，而且显著增加了认知下降速度较快的风险。性别和 Aβ 的交互作用主要局限于颞叶，但颞叶以外的 tau 性别差异突出了女性在出现临床症状时 tau 增殖加速的可能性。
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