Neurophysiological signatures in Alzheimer's disease are distinctly associated with TAU, amyloid-β accumulation, and cognitive decline

Kamalini G. Ranasinghe, Jungho Cha, Leonardo Iaccarino, Leighton B. Hinkley, Alexander J. Beagle, Julie Pham, William J. Jagust, Bruce L. Miller, Katherine P. Rankin, Gil D. Rabinovici, Keith A. Vossel, Srikantan S. Nagarajan

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53 Scopus citations


Neural synchrony is intricately balanced in the normal resting brain but becomes altered in Alzheimer's disease (AD). To determine the neurophysiological manifestations associated with molecular biomarkers of AD neuropathology, in patients with AD, we used magnetoencephalographic imaging (MEGI) and positron emission tomography with amyloid-beta (Aβ) and TAU tracers. We found that alpha oscillations (8 to 12 Hz) were hyposynchronous in occipital and posterior temporoparietal cortices, whereas delta-theta oscillations (2 to 8 Hz) were hypersynchronous in frontal and anterior temporoparietal cortices, in patients with AD compared to age-matched controls. Regional patterns of alpha hyposynchrony were unique in each neurobehavioral phenotype of AD, whereas the regional patterns of delta-theta hypersynchrony were similar across the phenotypes. Alpha hyposynchrony strongly colocalized with TAU deposition and was modulated by the degree of TAU tracer uptake. In contrast, delta-theta hypersynchrony colocalized with both TAU and Aβ depositions and was modulated by both TAU and A β tracer uptake. Furthermore, alpha hyposynchrony but not delta-theta hypersynchrony was correlated with the degree of global cognitive dysfunction in patients with AD. The current study demonstrates frequency-specific neurophysiological signatures of AD pathophysiology and suggests that neurophysiological measures from MEGI are sensitive indices of network disruptions mediated by TAU and Aβ and associated cognitive decline. These findings facilitate the pursuit of novel therapeutic approaches toward normalizing network synchrony in AD.

Original languageEnglish (US)
Article numbereaaz4069
JournalScience Translational Medicine
Issue number534
StatePublished - Mar 11 2020

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