Kamalini G Ranasinghe1, Cathrine Petersen1, Kiwamu Kudo2,3, Danielle Mizuiri2, Katherine P Rankin1, Gil D Rabinovici1,2, Maria Luisa Gorno-Tempini1, William W Seeley1,4, Salvatore Spina1, Bruce L Miller1, Keith Vossel1,5, Lea T Grinberg1,4,6, Srikantan S Nagarajan2. 1. Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, California, USA. 2. Department Radiology & Biomedical Imaging, University of California San Francisco, San Francisco, California, USA. 3. Medical Imaging Business Center, Ricoh Company, Ltd., Kanazawa, Japan. 4. Department of Pathology, University of California, San Francisco, San Francisco, California, USA. 5. Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. 6. Department of Pathology, LIM22, University of Sao Paulo, Sao Paulo, Brazil.
Abstract
INTRODUCTION: Neurophysiological manifestations selectively associated with amyloid beta and tau depositions in Alzheimer's disease (AD) are useful network biomarkers to identify peptide specific pathological processes. The objective of this study was to validate the associations between reduced neuronal synchrony within alpha oscillations and neurofibrillary tangle (NFT) density in autopsy examination, in patients with AD. METHODS: In a well-characterized clinicopathological cohort of AD patients (n = 13), we quantified neuronal synchrony within alpha (8-12 Hz) and delta-theta (2-8 Hz) oscillations, using magnetoencephalography during the disease course, within six selected neocortical and hippocampal regions, including angular gyrus, superior temporal gurus, middle frontal gyrus, primary motor cortex, CA1, and subiculum, and correlated these with regional NFT density quantified at histopathological examination. RESULTS: Abnormal synchrony in alpha, but not in delta-theta, significantly predicted the NFT density at post mortem neuropathological examination. DISCUSSION: Reduced alpha synchrony is a sensitive neurophysiological index associated with pathological tau, and a potential network biomarker for clinical trials, to gauge the extent of network dysfunction and the degree of rescue in treatments targeting tau pathways in AD.
INTRODUCTION: Neurophysiological manifestations selectively associated with amyloid beta and tau depositions in Alzheimer's disease (AD) are useful network biomarkers to identify peptide specific pathological processes. The objective of this study was to validate the associations between reduced neuronal synchrony within alpha oscillations and neurofibrillary tangle (NFT) density in autopsy examination, in patients with AD. METHODS: In a well-characterized clinicopathological cohort of AD patients (n = 13), we quantified neuronal synchrony within alpha (8-12 Hz) and delta-theta (2-8 Hz) oscillations, using magnetoencephalography during the disease course, within six selected neocortical and hippocampal regions, including angular gyrus, superior temporal gurus, middle frontal gyrus, primary motor cortex, CA1, and subiculum, and correlated these with regional NFT density quantified at histopathological examination. RESULTS: Abnormal synchrony in alpha, but not in delta-theta, significantly predicted the NFT density at post mortem neuropathological examination. DISCUSSION: Reduced alpha synchrony is a sensitive neurophysiological index associated with pathological tau, and a potential network biomarker for clinical trials, to gauge the extent of network dysfunction and the degree of rescue in treatments targeting tau pathways in AD.
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