Altered excitatory and inhibitory neuronal subpopulation parameters are distinctly associated with tau and amyloid in Alzheimer's disease

Background: Neuronal- and circuit-level abnormalities of excitation and inhibition are shown to be associated with tau and amyloid-beta (A beta) in preclinical models of Alzheimer's disease (AD). These relationships remain poorly understood in patients with AD. Methods: Using empirical spectra from magnetoencephalography and computational modeling (neural mass model), we examined excitatory and inhibitory parameters of neuronal subpopulations and investigated their specific associations to regional tau and A beta, measured by positron emission tomography, in patients with AD. Results: Patients with AD showed abnormal excitatory and inhibitory time-constants and neural gains compared to age-matched controls. Increased excitatory time-constants distinctly correlated with higher tau depositions while increased inhibitory time-constants distinctly correlated with higher A beta depositions. Conclusions: Our results provide critical insights about potential mechanistic links between abnormal neural oscillations and cellular correlates of impaired excitatory and inhibitory synaptic functions associated with tau and A beta in patients with AD.

Automated summary

This study investigated the associations between excitatory and inhibitory parameters and tau and A beta in patients with Alzheimer's disease (AD) using magnetoencephalography and computational modeling. The results showed abnormal excitatory and inhibitory time-constants in AD patients, which correlated with tau and A beta depositions.