Date of Award
2024
Degree Type
Dissertation
Degree Name
Doctor of Philosophy in Interdisciplinary Neuroscience
Department
Interdisciplinary Studies
First Advisor
John K. Robinson
Abstract
Sporadic, late-onset Alzheimer’s disease (LOAD) accounts for a staggering 98% of cases yet does not arise from a single genetic mutation. Rather, an extensive body of research has revealed that LOAD is likely the result of complex interactions between genetics and several lifestyle factors. There exists a substantial gap in understanding the mechanisms behind LOAD development and the impacts of lifestyle on disease progression. Enhanced rodent models may help elucidate mechanisms by which LOAD develops. This longitudinal study introduces a novel rat model of LOAD (CrAβ), created using CRISPR-Cas9 gene editing technology to express humanized Aβ. The effects of a western diet (WD) or treadmill running exercise intervention were examined using both operant and spatial learning and memory paradigms paired with histological analysis. While both control and CrAβ animals on WD resulted in diet-induced obesity, increased white adipose tissue, reduced HDL cholesterol, and increased triglycerides, only control animals yielded increased liver weights and impairments in behavioral domains. The lack of neuropathology in the CrAβ animals, absence of cognitive impairments, and static measurements on liver weights in these animals fed WD indicate they appear to be immune to its deleterious effects on liver health and subsequently on learning and memory. Although the mechanisms by which this protection occurs was not investigated in this study, the findings further support the theory of an alternative signaling pathway, likely leading to an inflammatory response which ultimately impairs cognition in our control animals. This work adds to a growing body of evidence which suggests cognitive impairments that arise from WD may not be solely due to the hypothesized mediation of diet on Aβ accumulation, but perhaps via alternative signaling mechanisms.
Recommended Citation
Mattar, Jennifer M., "EFFECTS OF WESTERN DIET OR EXERCISE EXPOSURE IN A NOVEL RAT MODEL OF LATE-ONSET ALZHEIMER’S DISEASE" (2024). Open Access Dissertations. Paper 1648.
https://digitalcommons.uri.edu/oa_diss/1648