Altered excitatory and inhibitory neuronal subpopulation parameters are distinctly associated with tau and amyloid in Alzheimer's disease

Kamalini G. Ranasinghe; Parul Verma; Chang Cai; Xihe Xie; Kiwamu Kudo; Xiao Gao; Hannah Lerner; Danielle Mizuiri; Amelia Strom; Leonardo Iaccarino; Renaud La Joie; Bruce L. Miller; Maria Luisa Gorno‐Tempini; Katherine P. Rankin; William J. Jagust; Keith A. Vossel; Gil Dan Rabinovici; Ashish Raj; Srikantan S. Nagarajan

doi:10.7554/elife.77850

NeuroscienceeLifeMay 20, 2022

Peer-reviewed journal article

Altered excitatory and inhibitory neuronal subpopulation parameters are distinctly associated with tau and amyloid in Alzheimer's disease

Kamalini G. Ranasinghe iD, Parul Verma iD, Chang Cai iD, Xihe Xie iD, Kiwamu Kudo iD, Xiao Gao iD, Hannah Lerner iD, Danielle Mizuiri iD, Amelia Strom iD, Leonardo Iaccarino iD, Renaud La Joie iD, Bruce L. Miller iD, Maria Luisa Gorno‐Tempini iD, Katherine P. Rankin iD, William J. Jagust iD, Keith A. Vossel iD, Gil Dan Rabinovici iD, Ashish Raj iD, Srikantan S. Nagarajan iD

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Abstract

BackgroundNeuronal and circuit level abnormalities of excitation and inhibition are shown to be associated with tau and amyloid-beta (A{beta}) in preclinical models of Alzheimers disease (AD). These relationships remain poorly understood in patients with AD. MethodsUsing empirical spectra from magnetoencephalography (MEG) and computational modeling (neural mass model; NMM) we examined excitatory and inhibitory parameters of neuronal subpopulations and investigated their specific associations to regional tau and A{beta}, measured by positron emission tomography (PET), in patients with AD. ResultsPatients 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 A{beta} depositions. ConclusionsOur 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 A{beta} in patients with AD. FundingThis 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 & GDR), R01 AG045611 (GDR); AG034570, AG062542 (WJ); NS100440 (SSN), DC176960 (SSN), DC017091 (SSN), AG062196 (SSN); a grant from John Douglas French Alzheimers Foundation (KAV); grants from Larry L. Hillblom Foundation: 2015-A-034-FEL and (KGR); 2019-A-013-SUP (KGR); a grant from the Alzheimers Association: (PCTRB-13-288476) (KAV), and made possible by Part the CloudTM, (ETAC-09-133596); a grant from Tau Consortium (GDR & WJJ), and a gift from the S. D. Bechtel Jr. Foundation.