Integrated transcriptomic and neuroimaging brain model decodes biological mechanisms in aging and Alzheimer's disease

被引：21

作者：

Adewale, Quadri ^{[1
,2
,3
]}

Khan, Ahmed F. ^{[1
,2
,3
]}

Carbonell, Felix ^{[4
]}

Iturria-Medina, Yasser ^{[1
,2
,3
]}

机构：

[1] McGill Univ, Montreal Neurol Inst, Neurol & Neurosurg Dept, Montreal, PQ, Canada

[2] McGill Univ, McConnell Brain Imaging Ctr, Montreal Neurol Inst, Montreal, PQ, Canada

[3] McGill Univ, Ludmer Ctr Neuroinformat & Mental Hlth, Montreal, PQ, Canada

[4] Biospect Inc, Montreal, PQ, Canada

来源：

ELIFE | 2021年 / 10卷

基金：

美国国家卫生研究院;

关键词：

AMYLOID-BETA; COGNITIVE FUNCTION; COUPLED RECEPTORS; SKELETAL-MUSCLE; GENE-EXPRESSION; RESTING-STATE; NETWORK; BLOOD; METABOLISM; TRIB3;

D O I：

10.7554/eLife.62589

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Both healthy aging and Alzheimer's disease (AD) are characterized by concurrent alterations in several biological factors. However, generative brain models of aging and AD are limited in incorporating the measures of these biological factors at different spatial resolutions. Here, we propose a personalized bottom-up spatiotemporal brain model that accounts for the direct interplay between hundreds of RNA transcripts and multiple macroscopic neuroimaging modalities (PET, MRI). In normal elderly and AD participants, the model identifies top genes modulating tau and amyloid-beta burdens, vascular flow, glucose metabolism, functional activity, and atrophy to drive cognitive decline. The results also revealed that AD and healthy aging share specific biological mechanisms, even though AD is a separate entity with considerably more altered pathways. Overall, this personalized model offers novel insights into the multiscale alterations in the elderly brain, with important implications for identifying effective genetic targets for extending healthy aging and treating AD progression.

引用

页数：22

共 112 条

[1] The Complex and Multifactorial Nature of Alzheimer's Disease [J].