A mechanistic model explains oscillatory slowing and neuronal hyperactivity in Alzheimer’s disease

Abstract

Alzheimer's disease is the most common cause of dementia and is linked to the spreading of pathological amyloid-β 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-β 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.

Brain Segregation and Integration Relate to Word-Finding Abilities in Older and Younger Adults

“…Resonance plays a crucial role in enabling synchronized activity and oscillatory patterns, and a disruption in the temporal coordination of neuronal activity may lead to cognitive impairments (Lehrer & Eddie, 2013;Uhlhaas & Singer, 2006). In conditions like Alzheimer's disease, even before disease onset, brain pathology may cause hyperactivity and/or inhibition of neurons, disrupting the neuronal excitation/inhibition (E/I) balance and affecting whole-brain network configurations (Alexandersen et al, 2022;Stam et al, 2023;van Nifterick et al, 2022). Our findings may suggest a similar disruption of the E/I balance in older adults experiencing word-finding difficulties.…”