Li Joyce S, Tun Samantha M, Ficek-Tani Bronte, Xu Wanwan, Wang Selena, Horien Corey L, Toyonaga Takuya, Nuli Shreya S, Zeiss Caroline J, Powers Albert R, Zhao Yize, Mormino Elizabeth C, Fredericks Carolyn A
Department of Neurology, Yale School of Medicine, New Haven, Connecticut.
University of Washington School of Medicine, Seattle, Washington.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Dec;9(12):1301-1311. doi: 10.1016/j.bpsc.2024.07.012. Epub 2024 Jul 25.
While the amygdala receives early tau deposition in Alzheimer's disease (AD) and is involved in social and emotional processing, the relationship between amygdalar tau and early neuropsychiatric symptoms in AD is unknown. We sought to determine whether focal tau binding in the amygdala and abnormal amygdalar connectivity were detectable in a preclinical AD cohort and identify relationships between these and self-reported mood symptoms.
We examined 598 individuals (347 amyloid positive [58% female], 251 amyloid negative [62% female] subset in tau positron emission tomography and functional magnetic resonance imaging cohorts) from the A4 (Anti-Amyloid Treatment in Asymptomatic AD) Study. In the tau positron emission tomography cohort, we used amygdalar segmentations to examine representative nuclei from 3 functional divisions of the amygdala. We analyzed between-group differences in division-specific tau binding in the amygdala in preclinical AD. We conducted seed-based functional connectivity analyses from each division in the functional magnetic resonance imaging cohort. Finally, we conducted exploratory post hoc correlation analyses between neuroimaging biomarkers of interest and anxiety and depression scores.
Amyloid-positive individuals demonstrated increased tau binding in the medial and lateral amygdala, and tau binding in these regions was associated with mood symptoms. Across amygdalar divisions, amyloid-positive individuals had relatively higher regional connectivity from the amygdala to other temporal regions, the insula, and the orbitofrontal cortex, but medial amygdala to retrosplenial cortex connectivity was lower. Medial amygdala to retrosplenial connectivity was negatively associated with anxiety symptoms, as was retrosplenial tau.
Our findings suggest that preclinical tau deposition in the amygdala and associated changes in functional connectivity may be related to early mood symptoms in AD.
虽然杏仁核在阿尔茨海默病（AD）中会较早出现tau蛋白沉积，且与社交和情感处理有关，但杏仁核tau蛋白与AD早期神经精神症状之间的关系尚不清楚。我们试图确定在临床前AD队列中是否可检测到杏仁核中的局灶性tau蛋白结合及异常的杏仁核连接性，并确定这些与自我报告的情绪症状之间的关系。
我们检查了来自A4（无症状AD的抗淀粉样蛋白治疗）研究的598名个体（tau正电子发射断层扫描和功能磁共振成像队列中，347名淀粉样蛋白阳性[58%为女性]，251名淀粉样蛋白阴性[62%为女性]）。在tau正电子发射断层扫描队列中，我们使用杏仁核分割来检查杏仁核3个功能分区的代表性核团。我们分析了临床前AD中杏仁核特定分区tau蛋白结合的组间差异。我们在功能磁共振成像队列中对每个分区进行基于种子点的功能连接分析。最后，我们对感兴趣的神经影像生物标志物与焦虑和抑郁评分进行了探索性的事后相关分析。
淀粉样蛋白阳性个体在内侧和外侧杏仁核中显示出tau蛋白结合增加，且这些区域的tau蛋白结合与情绪症状相关。在整个杏仁核分区中，淀粉样蛋白阳性个体从杏仁核到其他颞叶区域、脑岛和眶额皮质具有相对较高的区域连接性，但内侧杏仁核到压后皮质的连接性较低。内侧杏仁核到压后皮质的连接性与焦虑症状呈负相关，压后皮质的tau蛋白也是如此。
我们的研究结果表明，临床前杏仁核中的tau蛋白沉积及功能连接的相关变化可能与AD早期情绪症状有关。
