Synaptic Change, Sleep, and Pathological Analyses in Alzheimer’s Disease (2023)

Undergraduate: Kathryn Joyce

Faculty Advisor: Monica Gaudier-Diaz
Department: Cell Biology and Physiology, Psychology & Neuroscience

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease that leads to a marked loss of cortical and hippocampal synapses, presenting as a progressive loss of memories, motor function, changes in personality, and many other functions. Additionally, many patients report changes in their sleep patterns which may lead to the well-known night wandering phenotype. Due to the severity of AD worldwide, transgenic mouse models have been created to study the effects of known mutations in human amyloid precursor protein (APP), presenilin proteins (PSEN), and Tau protein. Based on preliminary data, a mouse model of Tauopathy was found to exhibit a breakdown of dark cycle sleep; therefore, we analyzed synaptic changes in PS19 animals in response to sleep disruption via Western Blotting. We also analyzed 5xFAD sleep behavior at 3-, 6-, and 11-month-old mice to understand amyloidal effects on sleep. To do this, we analyzed baseline sleep at all ages, along with two windows of sleep recovery after a four-hour sleep deprivation period, of male and female 5xFAD mice compared to their wildtype littermates. We found there to be a decrease in dark cycle sleep in older males, with no differences in sleep behavior after deprivation. Females exhibited within- and between-genotype differences in light cycle sleep at 3- and 6-months of age, while males did not. Following sleep recording via the Piezosleep system, we analyzed hippocampal inflammation, marked by TNFɑ and ILβ-1, of mice from each age group via quantitative PCR.

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