1. Profound degeneration of wake-promoting neurons in Alzheimer’s disease
- Author
-
Jun Oh, Helmut Heinsen, Jessica Kudlacek, William W. Seeley, Celica Cosme, Christine M. Walsh, Elisa de Paula França Resende, Thomas C. Neylan, Eduardo Joaquim Lopes Alho, Jackson C. Bittencourt, Rana Eser, Dulce Ovando Morales, Salvatore Spina, Bruce L. Miller, Cathrine Petersen, Lea T. Grinberg, Alexander J. Ehrenberg, Sara R. Dunlop, and Panos Theofilas
- Subjects
Male ,Sleep Wake Disorders ,0301 basic medicine ,Epidemiology ,Stereology ,Autopsy ,Degeneration (medical) ,Disease ,Article ,Progressive supranuclear palsy ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Developmental Neuroscience ,Alzheimer Disease ,Humans ,Medicine ,Corticobasal degeneration ,Aged ,Neurons ,business.industry ,Health Policy ,Brain ,Middle Aged ,medicine.disease ,eye diseases ,Psychiatry and Mental health ,030104 developmental biology ,Tauopathies ,Locus coeruleus ,Female ,Wakefulness ,Supranuclear Palsy, Progressive ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Neuroscience ,030217 neurology & neurosurgery ,AUTÓPSIA - Abstract
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.
- Published
- 2019