Uncovering the System Vulnerability and Criticality of Human Brain Under Dynamical Neuropathological Events in Alzheimer's Disease

Overview

Journal J Alzheimers Dis

Publisher Sage Publications

Specialties Geriatrics
Neurology

Date 2023 Sep 4

PMID 37661878

Authors

Jingwen Zhang

Qing Liu

Haorui Zhang

Michelle Dai

Qianqian Song

Defu Yang

Guorong Wu

Minghan Chen

Affiliations

Soon will be listed here.

Abstract

Background: Despite the striking efforts in investigating neurobiological factors behind the acquisition of amyloid-β (A), protein tau (T), and neurodegeneration ([N]) biomarkers, the mechanistic pathways of how AT[N] biomarkers spreading throughout the brain remain elusive.

Objective: To disentangle the massive heterogeneities in Alzheimer's disease (AD) progressions and identify vulnerable/critical brain regions to AD pathology.

Methods: In this work, we characterized the interaction of AT[N] biomarkers and their propagation across brain networks using a novel bistable reaction-diffusion model, which allows us to establish a new systems biology underpinning of AD progression. We applied our model to large-scale longitudinal neuroimages from the ADNI database and studied the systematic vulnerability and criticality of brains.

Results: Our model yields long term prediction that is statistically significant linear correlated with temporal imaging data, produces clinically consistent risk prediction, and captures the Braak-like spreading pattern of AT[N] biomarkers in AD development.

Conclusions: Our major findings include (i) tau is a stronger indicator of regional risk compared to amyloid, (ii) temporal lobe exhibits higher vulnerability to AD-related pathologies, (iii) proposed critical brain regions outperform hub nodes in transmitting disease factors across the brain, and (iv) comparing the spread of neuropathological burdens caused by amyloid-β and tau diffusions, disruption of metabolic balance is the most determinant factor contributing to the initiation and progression of AD.

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