Thursday, January 2, 2025
1/2/2025
Abstract Alzheimer's disease (AD) is a debilitating neurodegenerative disease responsible for cognitive impairment and dementia. An estimated 13 million Americans will suffer from AD by the year 2050. Approximately half of these individuals will suffer from sleep apnea. While sleep apnea is known to independently cause cognitive deficits, it also worsens AD. Sleep apnea facilitates early onset of AD and exacerbates AD associated dementia. Additionally, when sleep apnea is treated in AD patients, cognition is significantly improved. Despite evidence of strong links between sleep apnea and AD, there is a limited understanding into the mechanistic entanglement of these two conditions. This gap in knowledge likely contributes to the lack of effective therapies for AD and AD associated dementias. Our research addresses this issue by examining how intermittent hypoxia (IH), a primary consequence of sleep apnea, adversely effects AD neuropathology in an AD mouse model. Our work indicates that IH stimulates activity from the carotid bodies to increase hippocampal oxidative stress, which may worsen AD pathology. These new observations suggest that carotid bodies, the primary organs responsible for oxygen sensing, may serve as key regulators in causing IH- dependent changes associated with AD. We hypothesize that IH-dependent activity from the carotid bodies, causes oxidative stress, which in turn, promotes neurodegeneration and facilitates neuropathologies associated with AD. To test this, we developed a set of aims that: (1) examines the role of carotid body activity on hippocampal based-behavior and neurophysiology; and (2) determines how carotid body activity influences neurodegeneration and plaque formation in an AD mouse model exposed to IH. By defining how carotid body activity influences IH-dependent outcomes, our work establishes a new area of research that will identify systemic mechanisms promoting neurodegeneration and neuropathological changes that drive cognitive decline and dementia in AD. This work may lead to effective therapies needed to alleviate the burden of AD and AD related dementias for millions of Americans suffering from the disease.
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