Neurophysiological trajectories in Alzheimer's disease progression.

Alzheimer's disease (AD) is characterized by accumulation of amyloid- β and misfolded tau proteins causing synaptic dysfunction and progressive neurodegeneration and cognitive decline. Altered neural oscillations have been consistently demonstrated in AD. However, the trajectories of abnormal neural oscillations in AD progression and their relation to neurodegeneration and cognitive decline are unknown. We deployed robust event-based sequencing models (EBM) to investigate trajectories of long-range and local neural synchrony across AD stages, estimated from resting-state magnetoencephalography. Synchrony increases in delta-theta and decreases in alpha and beta bands showed progressive changes along the EBM stages of AD. Decreases in alpha and beta synchrony preceded both neurodegeneration and cognitive decline, indicating that frequency-specific neuronal synchrony abnormalities are early manifestations of AD pathophysiology. Long-range synchrony effects were larger than local synchrony, indicating greater sensitivity of connectivity metrics involving multiple brain regions. These results demonstrate the evolution of functional neuronal deficits along the sequence of AD progression.