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[Formula see text]) 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[Formula see text] and tau on the excitation-inhibition balance of the local nodes. RESULTS: We found a clear dominance of A[Formula see text] over tau in the early disease stages (MCI), while tau dominates over A[Formula see text] in the latest stages (AD). We identify crucial roles for A[Formula see text] 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.