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0089 Chronic sleep disruption increases amyloid beta deposition and gliosis in the 5xFAD mouse model

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Recent studies have found that mid-life sleep disruption is associated with the development of Alzheimer’s disease-related neuropathology, including the deposition of amyloid beta. Yet, the mechanism connecting sleep disruption, particularly… Click to show full abstract

Recent studies have found that mid-life sleep disruption is associated with the development of Alzheimer’s disease-related neuropathology, including the deposition of amyloid beta. Yet, the mechanism connecting sleep disruption, particularly over chronic timescales, and downstream Alzheimer’s pathology remains unclear. In this study, we evaluated the impact chronic sleep disruption has on the development of neuroinflammation and amyloid beta plaques in the 5xFAD amyloidosis mouse model. Chronic sleep disruption in male and female C57BL/6 and 5xFAD+ mice was performed in Lafayette sleep fragmentation cages from 10-18 weeks of age. Glymphatic function was assessed by measuring the influx of fluorescent cerebrospinal fluid tracers into brain tissue. Aquaporin-4 localization, amyloid-beta plaque deposition, and markers of astroglial and microglial activation were assessed by immunofluorescence. We observed that chronic sleep disruption increased neuropathological outcomes in 5xFAD+ and littermate controls. This was evident in significantly increased amyloid-beta plaque deposition and significantly increased gliosis, indicated by increases in both astrocyte (GFAP) and microglial (Iba1) expression. The impact on glymphatic function, evaluated through both cerebrospinal fluid tracer distribution and assessment of aquaporin-4 mislocalization, was assessed in parallel and correlated with neuropathological outcomes. These findings highlight the critical association between dysfunctional sleep and the development of Alzheimer’s-related amyloid beta pathology. They indicate that there is an interaction between chronic sleep disruption, neuroinflammation, and amyloid □ deposition.  

Keywords: amyloid beta; chronic sleep; sleep disruption; disruption; deposition; pathology

Journal Title: SLEEP
Year Published: 2023

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