Whole-brain modeling of the differential influences of Amyloid-Beta and Tau in Alzheimer’s Disease

Alzheimer’s Disease (AD) is a neurodegenerative condition associated with extra- and intra-neuronal accu- mulation of two misfolded proteins, namely Amyloid-Beta (Aβ) and tau. In this paper, we study the effect of these proteins on neuronal activity, with the aim of assessing their individual and combined impact on neuronal processes. The technique uses a whole-brain dynamic model to find the optimal parameters that best describe the effects of Aβ and tau on the excitation-inhibition balance of the local nodes. Our experimental results show a clear dominance of the neuronal activity of Aβ over tau in the early disease stages (Mild Cognitive Impairment), while tau dominates over Aβ in the latest stages (AD). Our findings identify a crucial role for Aβ and tau in contributing to complex neuronal dynamics and demonstrate the viability of using regional distributions of neuropathology to define models of large-scale brain function in AD. Our study provides further insight into the dynamics and complex interplay between these two proteins among themselves and with the regional neural activity, opening the path for further investigations on biomarkers and candidate therapeutic targets in-silico.