A mechanistic model explains oscillatory slowing and neuronal hyperactivity in Alzheimer's disease
Alzheimers disease is the most common cause of dementia and is linked to the spreading of pathological amyloid-{beta} and tau proteins throughout the brain. Recent studies have highlighted stark differences in how amyloid-{beta} and tau affect neurons at the cellular scale. On a larger scale, Alzheimers patients are observed to undergo a period of early-stage neuronal hyperactivation followed by neurodegeneration and frequency-slowing of neuronal oscillations. Herein, we model the spreading of both amyloid-{beta} and tau across a human connectome and investigate how the neuronal dynamics are affected by disease progression. By including the effects of both amyloid-{beta} and tau pathology, we find that our model explains AD-related frequency slowing, early-stage hyperactivation, and late-stage hypoactivation. By testing different hypotheses, we show that hyperactivation and frequency-slowing are not due to the topological interactions between different regions but are mostly the result of local neurotoxicity induced by amyloid-{beta} and tau protein.