Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, United States; Medical Imaging Business Center, Ricoh Company, Kanazawa, Japan
Xiao Gao
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, United States
Hannah Lerner
Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, United States
Danielle Mizuiri
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, United States
Amelia Strom
Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, United States
Leonardo Iaccarino
Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, United States
Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States
Keith Vossel
Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, United States; Mary S. Easton Center for Alzheimer’s Disease Research, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
Gil D Rabinovici
Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, United States; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, United States
Background: Neuronal- and circuit-level abnormalities of excitation and inhibition are shown to be associated with tau and amyloid-beta (Aβ) in preclinical models of Alzheimer’s disease (AD). These relationships remain poorly understood in patients with AD. Methods: Using empirical spectra from magnetoencephalography and computational modeling (neural mass model), we examined excitatory and inhibitory parameters of neuronal subpopulations and investigated their specific associations to regional tau and Aβ, measured by positron emission tomography, in patients with AD. Results: Patients with AD showed abnormal excitatory and inhibitory time-constants and neural gains compared to age-matched controls. Increased excitatory time-constants distinctly correlated with higher tau depositions while increased inhibitory time-constants distinctly correlated with higher Aβ depositions. Conclusions: Our results provide critical insights about potential mechanistic links between abnormal neural oscillations and cellular correlates of impaired excitatory and inhibitory synaptic functions associated with tau and Aβ in patients with AD. Funding: This study was supported by the National Institutes of Health grants: K08AG058749 (KGR), F32AG050434-01A1 (KGR), K23 AG038357 (KAV), P50 AG023501, P01 AG19724 (BLM), P50-AG023501 (BLM and GDR), R01 AG045611 (GDR); AG034570, AG062542 (WJ); NS100440 (SSN), DC176960 (SSN), DC017091 (SSN), AG062196 (SSN); a grant from John Douglas French Alzheimer’s Foundation (KAV); grants from Larry L. Hillblom Foundation: 2015-A-034-FEL (KGR), 2019-A-013-SUP (KGR); grants from the Alzheimer’s Association: AARG-21-849773 (KGR); PCTRB-13-288476 (KAV), and made possible by Part the CloudTM (ETAC-09-133596); a grant from Tau Consortium (GDR and WJJ), and a gift from the S. D. Bechtel Jr. Foundation.
