O2‐05‐02: Potential role of the sleep‐wake cycle in the pathogenesis of Alzheimer's disease
Year: 2012
Type: article
Abstract: Age-related aggregation of amyloid-β (Aβ) is an upstream pathologic event before the clinical onset of Alzheimer's disease (AD). In the brains of mice, interstitial fluid (ISF) Aβ levels increase during wakefulness and decrease during sleep prior to Aβ aggregation. The amount and quality of sleep declines with aging and to a greater extent in AD. How the amount and quality of sleep as well as the diurnal fluctuation in Aβ changes with age and Aβ aggregation are not well understood. The sleep-wake cycle and diurnal fluctuation of ISF Aβ in two different brain regions (hippocampus and striatum) which have different vulnerabilities to Aβ pathology were investigated in APPswe/PS1δE9 mice at 3, 6, and 9 months. Active immunization with Aβ42 was performed in young APPswe/PS1δE9 mice and the sleep-wake cycle and ISF Aβ were analyzed at 9 months. Diurnal fluctuation of ISF Aβ was present in two different brain regions with a normal sleep-wake cycle before Aβ plaque formation. By six months, when the Aβ plaques begin to deposit in the hippocampus but not in the striatum, the diurnal fluctuation of ISF Aβ in the hippocampus was attenuated. At nine months, when the Aβ plaques first begin to form in the striatum, the loss in the diurnal fluctuation of ISF Aβ was observed in both brain areas with a marked deterioration of the sleep-wake cycle. Actively immunized APPswe/PS1δE9mice had markedly decreased Aβ deposits in the brain at 9 months and showed a normal sleep-wake cycle and normal diurnal fluctuation of ISF Aβ. Aggregation of Aβ appears to disrupt the sleep-wake cycle as well as the diurnal fluctuation of ISF Aβ in the mouse brain. Sleep-wake behavior and loss of diurnal fluctuation of Aβ in the CNS are useful functional and diagnostic markers for the progression of AD pathology.
Source: Alzheimer s & Dementia
Authors: Jee Hoon Roh, Floy Stewart, David Holtzman
Institution: Washington University in St. Louis
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2050137876