Analyzing the Spatiotemporal Interaction and Propagation of ATN Biomarkers in Alzheimer's Disease using Longitudinal Neuroimaging Data

TL;DR

This study investigates the spatiotemporal progression and interactions of Alzheimer's disease biomarkers using longitudinal neuroimaging data, revealing distinct propagation patterns and regional associations of amyloid, tau, and neurodegeneration.

Contribution

It introduces a comprehensive analysis of the temporal and spatial dynamics of ATN biomarkers, including modeling their interactions and propagation patterns in the brain.

Findings

Amyloid buildup precedes tau and neurodegeneration with a temporal latency.

Amyloid propagates along the brain's topological network.

Tau and neurodegeneration show strong regional association.

Abstract

Three major biomarkers: beta-amyloid (A), pathologic tau (T), and neurodegeneration (N), are recognized as valid proxies for neuropathologic changes of Alzheimer's disease. While there are extensive studies on cerebrospinal fluids biomarkers (amyloid, tau), the spatial propagation pattern across brain is missing and their interactive mechanisms with neurodegeneration are still unclear. To this end, we aim to analyze the spatiotemporal associations between ATN biomarkers using large-scale neuroimaging data. We first investigate the temporal appearances of amyloid plaques, tau tangles, and neuronal loss by modeling the longitudinal transition trajectories. Second, we propose linear mixed-effects models to quantify the pathological interactions and propagation of ATN biomarkers at each brain region. Our analysis of the current data shows that there exists a temporal latency in the build-up of amyloid to the onset of tau pathology and neurodegeneration. The propagation pattern of amyloid can be characterized by its diffusion along the topological brain network. Our models provide sufficient evidence that the progression of pathological tau and neurodegeneration share a strong regional association, which is different from amyloid.