Whole-brain modeling of the differential influences of amyloid-beta and tau in Alzheimer's disease

Abstract

Background. Alzheimer’s disease is a neurodegenerative condition associated with the accumulation of two misfolded proteins, amyloid-beta (A) and tau. We study their effect on neuronal activity, with the aim of assessing their individual and combined impact.

Methods. We use a whole-brain dynamic model to find the optimal parameters that best describe the effects of A and tau on the excitation-inhibition balance of the local nodes.

Results. We found a clear dominance of A over tau in the early disease stages (MCI), while tau dominates over A in the latest stages (AD). We identify crucial roles for A and tau in complex neuronal dynamics and demonstrate the viability of using regional distributions to define models of large-scale brain function in AD.

Conclusions. Our study provides further insight into the dynamics and complex interplay between these two proteins, opening the path for further investigations on biomarkers and candidate therapeutic targets in-silico.