ABSTRACT
INTRODUCTION The 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.
METHODS We tested competing mathematical models of network spread, aggregation, and amyloid-tau interactions on publicly available data from ADNI.
RESULTS Although 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.
DISCUSSION This 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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Updated manuscript and supplement, with separate figure files
