Tau and amyloid beta (Aβ) proteins accumulate along neuronal circuits in Alzheimer's disease. Unraveling the genetic background for the regional vulnerability of these proteinopathies can help in understanding the mechanisms of pathology progression. To that end, we developed a novel graph theory approach and used it to investigate the intersection of longitudinal Aβ and tau positron emission tomography imaging of healthy adult individuals and the genetic transcriptome of the Allen Human Brain Atlas. We identified distinctive pathways for tau and Aβ accumulation, of which the tau pathways correlated with cognitive levels. We found that tau propagation and Aβ propagation patterns were associated with a common genetic profile related to lipid metabolism, in which APOE played a central role, whereas the tau-specific genetic profile was classified as 'axon related' and the Aβ profile as 'dendrite related'. This study reveals distinct genetic profiles that may confer vulnerability to tau and Aβ in vivo propagation in the human brain.

中文翻译：

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对淀粉样β和tau在人类皮质中传播的神经遗传学贡献。

Tau和淀粉样β（Aβ）蛋白在阿尔茨海默氏病中沿神经元回路积聚。揭示这些蛋白病的区域易损性的遗传背景可以帮助理解病理学进展的机制。为此，我们开发了一种新颖的图论方法，并将其用于研究健康成年人的纵向Aβ和tau正电子发射断层扫描成像与Allen人脑图谱的基因转录组的交集。我们确定了tau和Aβ积累的独特途径，其中tau途径与认知水平相关。我们发现tau繁殖和Aβ繁殖模式与脂质代谢相关的常见遗传特征有关，其中APOE发挥了核心作用，而tau特异的遗传图谱被分类为“轴突相关”，而Aβ谱图被分类为“树突相关”。这项研究揭示了不同的遗传特征，这些遗传特征可能会使人脑中tau和Aβ体内繁殖易受伤害。