Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, United States; Medical Imaging Business Center, Ricoh Company Ltd, Kanazawa, Japan
Memory and Aging Center,UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States
Hirofumi Morise
Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, United States; Medical Imaging Business Center, Ricoh Company Ltd, Kanazawa, Japan
Faatimah Syed
Memory and Aging Center,UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States
Kensuke Sekihara
Signal Analysis Inc, Hachioji, Japan
Katherine P Rankin
Memory and Aging Center,UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States
Bruce L Miller
Memory and Aging Center,UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States
Joel H Kramer
Memory and Aging Center,UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States
Gil D Rabinovici
Memory and Aging Center,UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, United States
Keith Vossel
Memory and Aging Center,UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States; Mary S. Easton Center for Alzheimer’s Research and Care, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
Heidi E Kirsch
Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, United States
Alzheimer’s disease (AD) is characterized by the 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 relationship to neurodegeneration and cognitive decline are unknown. Here, we deployed robust event-based sequencing models (EBMs) to investigate the trajectories of long-range and local neural synchrony across AD stages, estimated from resting-state magnetoencephalography. The increases in neural synchrony in the delta-theta band and the decreases in the alpha and beta bands showed progressive changes throughout the stages of the EBM. Decreases in alpha and beta band synchrony preceded both neurodegeneration and cognitive decline, indicating that frequency-specific neuronal synchrony abnormalities are early manifestations of AD pathophysiology. The long-range synchrony effects were greater than the local synchrony, indicating a greater sensitivity of connectivity metrics involving multiple regions of the brain. These results demonstrate the evolution of functional neuronal deficits along the sequence of AD progression.
