Profound degeneration of wake-promoting neurons in Alzheimer's disease

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Oh, Jun ^{[1, 2]} ; Eser, Rana A. ^{[1, 2]} ; Ehrenberg, Alexander J. ^{[3, 1, 2]} ; Morales, Dulce ^[2] ; Petersen, Cathrine ^{[1, 2]} ; Kudlacek, Jessica ^[2] ; Dunlop, Sara R. ^{[2, 4]} ; Theofilas, Panos ^[2] ; Resende, Elisa D. P. F. ^{[5, 2]} ; Cosme, Celica ^[2] ; Alho, Eduardo J. L. ^[6] ; Spina, Salvatore ^[2] ; Walsh, Christine M. ^[2] ; Miller, Bruce L. ^{[5, 2]} ; Seeley, William W. ^[2] ; Bittencourt, Jackson C. ^{[7, 8]} ; Neylan, Thomas C. ^[9] ; Heinsen, Helmut ^{[10, 11]} ; Grinberg, Lea T. ^{[10, 5, 2, 12]}

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^[1] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 - USA

^[2] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, Weill Inst Neurosci, San Francisco, CA 94143 - USA

^[3] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 - USA

^[4] Northwestern Univ, Dept Neurol, Chicago, IL 60611 - USA

^[5] Univ Calif San Francisco, Global Brain Hlth Inst, San Francisco, CA 94143 - USA

^[6] Univ Sao Paulo, Dept Neurol, Med Sch, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo - Brazil

^[8] Univ Sao Paulo, Ctr Neurosci & Behav, Inst Psychol, Sao Paulo - Brazil

^[9] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA - USA

^[10] Univ Sao Paulo, Dept Pathol, Med Sch, Sao Paulo - Brazil

^[11] Univ Wurzburg, Dept Psychiat, Wurzburg - Germany

^[12] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 - USA

• Tipo de documento: Artigo Científico
• Fonte: ALZHEIMERS & DEMENTIA; v. 15, n. 10, p. 1253-1263, OCT 2019.
• Citações Web of Science: 0

Resumo

Introduction: Sleep-wake disturbances are a common and early feature in Alzheimer's disease (AD). The impact of early tau pathology in wake-promoting neurons (WPNs) remains unclear. Methods: We performed stereology in postmortem brains from AD individuals and healthy controls to identify quantitative differences in morphological metrics in WPNs. Progressive supranuclear palsy (PSP) and corticobasal degeneration were included as disease-specific controls. Results: The three nuclei studied accumulate considerable amounts of tau inclusions and showed a decrease in neurotransmitter-synthetizing neurons in AD, PSP, and corticobasal degeneration. However, substantial neuronal loss was exclusively found in AD. Discussion: WPNs are extremely vulnerable to AD but not to 4 repeat tauopathies. Considering that WPNs are involved early in AD, such degeneration should be included in the models explaining sleep-wake disturbances in AD and considered when designing a clinical intervention. Sparing of WPNs in PSP, a condition featuring hyperinsomnia, suggest that interventions to suppress the arousal system may benefit patients with PSP. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 16/02224-1 - A existência da neurogênese durante o período da lactação
• Beneficiário: Jackson Cioni Bittencourt
• Modalidade de apoio: Auxílio à Pesquisa - Temático