A multi-scale model explains oscillatory slowing and neuronal hyperactivity in Alzheimer's disease

Alzheimer's 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, Alzheimer's 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.

Automated summary

Alzheimer's disease, characterized by the spreading of pathological amyloid-beta and tau proteins in the brain, is the leading cause of dementia. Recent studies have shown distinct effects of amyloid-beta and tau on neurons at the cellular level. At a larger scale, Alzheimer's patients experience early-stage neuronal hyperactivation followed by neurodegeneration and frequency slowing. Through modeling the spreading of both amyloid-beta and tau in a human connectome, this study investigates the impact of disease progression on neuronal dynamics. The results indicate that the model explains AD-related frequency slowing, early-stage hyperactivation, and late-stage hypoactivation by considering the effects of amyloid-beta and tau pathology. Moreover, the hyperactivation and frequency slowing are found to be mainly caused by local neurotoxicity induced by amyloid-beta and tau proteins rather than topological interactions between brain regions.