High-frequency EEG activity moderates the association between amyloid burden and tau in cognitively normal adults

Background: Resting electroencephalogram (EEG) may capture early excitatory-inhibitory (E-I) imbalance in Alzheimer's disease, but its relationship to beta-amyloid and tau in cognitively normal adults is unclear. Methods: We analyzed resting-state EEG from 24 older adults, 21 cognitively normal (13 beta-amyloid-negative, 8 beta-amyloid-positive) and 3 with MCI/AD (all beta-amyloid-positive), with beta-amyloid positron emission tomography (PET); 20 of the cognitively normal adults also had tau PET. Four parietal measures related to E-I balance and excitability (periodic gamma power, alpha-gamma and theta-gamma phase-amplitude coupling [PAC], and the aperiodic exponent) were related to beta-amyloid burden and to early medial temporal lobe (MTL) tau, adjusting for age and sex. Results: In 21 cognitively normal adults, higher beta-amyloid burden was associated with higher parietal periodic gamma power (beta= +0.50, p = 0.025). No E-I measure was associated with MTL tau across all participants. However, in beta-amyloid-positive adults, higher periodic gamma was associated with higher MTL tau, most strongly in the entorhinal cortex (beta = +0.90, p = 0.002), with no association in beta-amyloid-negative adults. Importantly, periodic gamma also moderated the association between beta-amyloid and MTL tau (p = 0.012; consistent across MTL regions after FDR correction). Conclusions: In this pilot study, parietal periodic gamma, an EEG marker of cortical excitability, increased with beta-amyloid burden and was related to MTL tau only in the presence of beta-amyloid. Periodic gamma is a candidate marker of beta-amyloid-related E-I imbalance that warrants confirmation in larger samples.