Lewis Honors College Capstone Collection

Year of Publication

2021

College

Arts and Sciences

Department/School/Program

Biology

Degree Name

Bachelor of Science in Biology

First Capstone/Thesis Advisor

Dr. Marilyn Duncan

Abstract

Alzheimer’s Disease (AD) is a neurodegenerative disease that is characterized by amyloid-beta (Aβ) plaques, neurofibrillary tangles, neuronal death, and profound cognitive impairment. Previous studies have indicated that increased Aβ and alterations in the daily sleep-wake cycle are early risk factors and possible predictors of AD. Acute sleep deprivation decreases Aβ clearance, and increased Aβ levels stimulate neuroinflammation and accelerate loss of neurons and synapses. Likewise, it has been shown that there are higher rates of sleep disorders in AD patients. However, limited studies have investigated whether sleep fragmentation accelerates the progression of AD pathology. This partial review will discuss experiments investigating the link between sleep and AD. Additionally, we completed three pilot studies exploring whether chronic disruption of daily sleep-wake cycles with sleep fragmentation (SF) increases Aβ and neuroinflammation in the brains of transgenic mice that serve as an experimental model for AD. Mice were sorted into an undisturbed sleep (US) group and an SF group, involving stimulation for one-hour periods during the light phase, 4 times/day, 5 days/week for 4 weeks. Sleep monitoring using the noninvasive piezoelectric system showed that the US mice slept as expected during the light phase; however, SF mice had greatly reduced sleep during the SF intervals, and sleep loss was only partially restored during the dark period. Protein analysis showed that hippocampal levels of Aβ40 and Aβ42 were significantly increased in SF compared to US mice. Additionally, gene expression markers of neuroinflammation in the hippocampus were significantly elevated in SF mice. These results suggest that fragmentation of the daily sleep-wake cycle stimulates hippocampal levels of Aβ and neuroinflammation. If future rodent studies support these findings that chronic SF advances AD pathology, then improving sleep consolidation would be a potential therapeutic strategy for reducing the progression of AD in humans.

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