Year: 2023
Type: dissertation
Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease that is growing in prevalence with an aging population. Along with cognitive impairments, AD patients experience a multitude of symptoms and comorbidities, including sleep and metabolic impairments such type II diabetes (T2D). Despite the rising incidence of AD, the connections and mechanisms connecting AD pathogenesis, sleep impairments, and metabolic dysfunction are widely unknown. This thesis provides insight into these relationships, with a focus on AD related tau pathology using the P301S PS19 mouse model of tauopathy. Specifically, we determine how age and tau pathology alter peripheral and cerebral metabolism. Next, we assess how tau pathology disrupts sleep quality and quantity. Collectively, we determined that tau pathology alters neuronal activity such that time spent awake is increased, while NREM and REM are decreased. Further, we explored how tau pathology alters relative spectral power. We found alterations in theta and beta frequencies. Relative delta power is also altered differentially when compared to wildtype (WT) mice. Tau pathology increases peripheral glucose sensitivity and while conserving cerebral ISF glucose and lactate fluctuations through stages of neurodegeneration. This study provides the foundation for future studies to explore mechanistic alterations and potential therapeutic advances relevant to AD and other tauopathies.
Author: Irmen, Riley Emma
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7017346504