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bioRxiv · 10.1101/2024.03.05.583407

Understanding the complex interplay between tau, amyloid and the network in the spatiotemporal progression of Alzheimer's Disease

Raj, A.·Torok, J.
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Abstract

INTRODUCTIONThe interaction of amyloid and tau in neurodegenerative diseases is a central feature of AD pathophysiology. While experimental studies point to various interaction mechanisms, their causal direction and mode (local, remote or network-mediated) remain unknown in human subjects. The aim of this study was to compare mathematical reaction-diffusion models encoding distinct cross-species couplings to identify which interactions were key to model success. METHODSWe tested competing mathematical models of network spread, aggregation, and amyloid-tau interactions on publicly available data from ADNI. RESULTSAlthough network spread models captured the spatiotemporal evolution of tau and amyloid in human subjects, the model including a one-way amyloid-to-tau aggregation interaction performed best. DISCUSSIONThis mathematical exposition of the "pas de deux" of co-evolving proteins provides quantitative, whole-brain support to the concept of amyloid-facilitated-tauopathy rather than the classic amyloid-cascade or pure-tau hypotheses, and helps explain certain known but poorly understood aspects of AD.

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Raj, A., Torok, J.. 2024-03-11. Understanding the complex interplay between tau, amyloid and the network in the spatiotemporal progression of Alzheimer's Disease. https://doi.org/10.1101/2024.03.05.583407

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