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

Authors
  • Oh, Jun1
  • Eser, Rana A1
  • Ehrenberg, Alexander J2
  • Morales, Dulce3
  • Petersen, Cathrine1
  • Kudlacek, Jessica3
  • Dunlop, Sara R4
  • Theofilas, Panos3
  • Resende, Elisa D P F5
  • Cosme, Celica3
  • Alho, Eduardo J L6
  • Spina, Salvatore3
  • Walsh, Christine M3
  • Miller, Bruce L5
  • Seeley, William W3
  • Bittencourt, Jackson C7
  • Neylan, Thomas C8
  • Heinsen, Helmut9
  • Grinberg, Lea T10
  • 1 Memory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
  • 2 Memory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; Department of Integrative Biology, University of California, Berkeley, Berkeley, CA, USA.
  • 3 Memory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • 4 Memory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, Northwestern University, Chicago, IL, USA.
  • 5 Memory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Global Brain Health Institute, University of California, San Francisco, San Francisco, CA, USA.
  • 6 Department of Neurology, University of Sao Paulo Medical School, Sao Paulo, Brazil. , (Brazil)
  • 7 Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil; Center for Neuroscience and Behavior, Institute of Psychology, University of Sao Paulo, Sao Paulo, Brazil. , (Brazil)
  • 8 Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.
  • 9 Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil; Department of Psychiatry, University of Wuerzburg, Wuerzburg, Germany. , (Brazil)
  • 10 Memory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Global Brain Health Institute, University of California, San Francisco, San Francisco, CA, USA; Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: [email protected] , (Brazil)
Type
Published Article
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
Publication Date
Oct 01, 2019
Volume
15
Issue
10
Pages
1253–1263
Identifiers
DOI: 10.1016/j.jalz.2019.06.3916
PMID: 31416793
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. 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. 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. 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. Copyright © 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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