背景:虽然杏仁核在阿尔茨海默病(AD)中接受早期tau沉积,并参与社交和情绪处理,杏仁核与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队列中是否可以检测到杏仁核中的局灶性tau结合和杏仁核连接异常,并确定这些与自我报告的情绪症状之间的关系。
方法:我们检查了n=598名个体(n=347名淀粉样蛋白阳性(58%为女性),n=来自A4研究的251个淀粉样蛋白阴性(62%女性);tauPET和fMRI队列的子集)。在我们的tauPET队列中,我们使用杏仁核分割来检查杏仁核的三个功能分区中的代表性细胞核。我们分析了临床前AD中杏仁核中分裂特异性tau结合的组间差异。我们对fMRI队列中的每个部门进行了基于种子的功能连接分析。最后,我们在感兴趣的神经影像学生物标志物与焦虑和抑郁评分之间进行了探索性事后相关性分析.
结果:淀粉样蛋白阳性个体在内侧和外侧杏仁核中表现出增加的tau结合(F(4,442)=14.61,p=0.00045;F(4,442)=5.83,p=0.024,分别)。穿过杏仁核分裂,淀粉样蛋白阳性个体从杏仁核到其他颞区的区域连通性相对增加,脑岛,和眶额皮质.内侧和外侧杏仁核中的tau结合与焦虑之间存在淀粉样蛋白组的相互作用。杏仁核内侧与脾后连接与焦虑症状呈负相关(rs=-0.103,p=0.015)。
结论:我们的研究结果表明,杏仁核中的临床前tau沉积可能导致功能连接发生有意义的变化,这可能使患者容易出现情绪症状。
BACKGROUND: 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.
METHODS: We examined n=598 individuals (n=347 amyloid-positive (58% female), n=251 amyloid-negative (62% female); subset into tau PET and fMRI cohorts) from the A4 Study. In our tau PET cohort, we used amygdalar segmentations to examine representative nuclei from three 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 fMRI cohort. Finally, we conducted exploratory post-hoc correlation analyses between neuroimaging biomarkers of interest and anxiety and depression scores.
RESULTS: Amyloid-positive individuals demonstrated increased tau binding in medial and lateral amygdala (F(4,442)=14.61, p=0.00045; F(4,442)=5.83, p=0.024, respectively). Across amygdalar divisions, amyloid-positive individuals had relatively increased regional connectivity from amygdala to other temporal regions, insula, and orbitofrontal cortex. There was an interaction by amyloid group between tau binding in the medial and lateral amygdala and anxiety. Medial amygdala to retrosplenial connectivity negatively correlated with anxiety symptoms (rs=-0.103, p=0.015).
CONCLUSIONS: Our findings suggest that preclinical tau deposition in the amygdala may result in meaningful changes in functional connectivity which may predispose patients to mood symptoms.