Regionally heterogeneous gamma alterations and their diagnostic value in early-onset Alzheimer's disease

Growing evidence links amyloid accumulation to altered gamma activity, positioning gamma oscillations as a promising biomarker for Alzheimer's pathology. We examined resting state gamma activity in early-onset Alzheimer's disease (EOAD) patients confirmed by CSF biomarkers. We aim to provide a holistic view of gamma activity patterns in EOAD by integrating structural and functional neuroimaging. In this cross-sectional study, we compared gamma power and coherence-total gamma (30-48 Hz), and sub-bands (gamma-1: 30-35 Hz; gamma-2: 35-40 Hz; gamma-3: 40-48 Hz)- alongside gray matter volumes in EOAD patients (N = 24) and matched healthy controls (N = 24). We further assessed gamma-related changes in relation to CSF biomarkers, cognitive performance, and structural brain alterations. Finally, discriminant analysis evaluated classification performance of these measures. EOAD patients showed increased gamma power, with region-specific increases and decreases in coherence. Frontal gray matter volume negatively correlated with coherence, whereas posterior volumes showed positive correlations. A combined model of parietal gamma power and coherence achieved 83.3% classification accuracy, with a cross-validated accuracy of 77.1% (ROC-AUC = 0.844). Overall, we showed that the gamma activity does not follow a strict pattern in EOAD pathology. Gamma power is elevated, whereas connectivity patterns vary by brain region, closely mirroring structural brain alterations. These findings underscore the relevance of gamma activity in Alzheimer's research and open new avenues for future investigation. CLINICAL TRIAL REGISTRATION NUMBER: NCT05989087. NAME OF THE TRIAL REGISTRY: The Resting-state EEG Gamma Oscillations in Alzheimer's Disease.