학술논문

Whole-brain modeling of the differential influences of amyloid-beta and tau in Alzheimer’s disease
Document Type
article
Source
Alzheimer’s Research & Therapy, Vol 15, Iss 1, Pp 1-18 (2023)
Subject
Alzheimer’s disease
Amyloid-beta
Tau
Whole-brain model
Simulation
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Language
English
ISSN
1758-9193
Abstract
Abstract Background Alzheimer’s disease is a neurodegenerative condition associated with the accumulation of two misfolded proteins, amyloid-beta (A $$\beta$$ β ) 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 $$\beta$$ β and tau on the excitation-inhibition balance of the local nodes. Results We found a clear dominance of A $$\beta$$ β over tau in the early disease stages (MCI), while tau dominates over A $$\beta$$ β in the latest stages (AD). We identify crucial roles for A $$\beta$$ β 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.