Functional Connectivity Hypersynchronization in Relatives of Alzheimer’s Disease Patients: An Early E/I Balance Dysfunction?

Alzheimer's disease (AD) studies on animal models, and humans showed a tendency of the brain tissue to become hyperexcitable and hypersynchronized, causing neurodegeneration. However, we know little about either the onset of this phenomenon or its early effects on functional brain networks. We studied functional connectivity (FC) on 127 participants (92 middle-age relatives of AD patients and 35 age-matched nonrelatives) using magnetoencephalography. FC was estimated in the alpha band in areas known both for early amyloid accumulation and disrupted FC in MCI converters to AD. We found a frontoparietal network (anterior cingulate cortex, dorsal frontal, and precuneus) where relatives of AD patients showed hypersynchronization in high alpha (not modulated by APOE-ε4 genotype) in comparison to age-matched nonrelatives. These results represent the first evidence of neurophysiological events causing early network disruption in humans, opening a new perspective for intervention on the excitation/inhibition unbalance.