The quest to comprehend genetic, biological, and symptomatic heterogeneity underlying Alzheimer's disease (AD) requires a deep understanding of mechanisms affecting complex brain systems. Neuroimaging genetics is an emerging field that provides a powerful way to analyze and characterize intermediate biological phenotypes of AD. Here, we describe recent studies showing the differential effect of genetic risk factors for AD on brain functional connectivity in cognitively normal, preclinical, prodromal, and AD dementia individuals. Functional neuroimaging genetics holds particular promise for the characterization of preclinical populations; target populations for disease prevention and modification trials. To this end, we emphasize the need for a paradigm shift towards integrative disease modeling and neuroimaging biomarker-guided precision medicine for AD and other neurodegenerative diseases.

中文翻译：

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阿尔茨海默病静息态功能神经影像遗传学的革命


要理解阿尔茨海默病 (AD) 背后的遗传、生物学和症状异质性，需要深入了解影响复杂大脑系统的机制。神经影像遗传学是一个新兴领域，它提供了一种强大的方法来分析和表征 AD 的中间生物表型。在这里，我们描述了最近的研究，这些研究表明 AD 遗传风险因素对认知正常、临床前、前驱和 AD 痴呆个体的大脑功能连接有不同的影响。功能性神经影像遗传学对于临床前群体的表征具有特殊的前景。疾病预防和改造试验的目标人群。为此，我们强调需要针对 AD 和其他神经退行性疾病进行综合疾病建模和神经影像生物标志物引导的精准医学的范式转变。