Electroencephalography neurophysiology alterations in association with Aβ and tau pathology across the symptomatic stages of Alzheimer’s disease continuum: a cross-sectional study

BACKGROUND: Amyloid-β (Aβ) and tau deposition drive Alzheimer's disease (AD). However, how these proteinopathies are linked to macroscopic neural activity alterations measured by electroencephalography (EEG) in symptomatic AD remains inadequately characterized. This study aims to investigate the associations between Aβ, tau, EEG neurophysiology, and cognition. METHODS: We conducted a cross-sectional study of 73 MCI and AD participants, who underwent resting-state EEG, Aβ-PET, and tau-PET. EEG source analysis was performed to extract regional spectral power. Linear mixed-effects models were used to examine the associations of regional Aβ (quantified by SUVR), tau (binary classification), with EEG features, controlling for age, sex and education. Ordinary least squares (OLS) regression was applied to investigate the relationships of EEG spectral power and global Aβ burden with cognitive performance. RESULTS: Elevated Aβ burden was associated with distinct regional spectral alterations. Specifically, higher Aβ SUVR was significantly correlated with increased theta power and decreased beta power in a subset of cortical regions. Tau positivity did not modulate the amyloid-theta association in any region, but attenuated the amyloid-beta association in a small set of parietal regions. CONCLUSIONS: We identified a localized pattern of Aβ-related neurophysiological dysfunction across the symptomatic stages of AD continuum, characterized by theta increases and beta decreases, supporting a robust association between Aβ burden and cortical neural slowing. The findings highlight the value of source-localized EEG power as a sensitive indicator of Aβ-associated network dysfunction in AD and underscore the potential of source-localized EEG as a complementary, non-invasive biomarker for assessing pathological burden and informing diagnostic strategies in AD.