A Model of Sporadic Late-Onset Alzheimer’s Disease in Humanized APP & APOE ε4 Knock-in Mice Raised on a High-Sucrose Diet
| dc.contributor.advisor | Bekar, Lane K | |
| dc.contributor.committeeMember | Taghibiglou, Changiz | |
| dc.contributor.committeeMember | Sawicki, Grzegorz | |
| dc.contributor.committeeMember | Mousseau, Darrell | |
| dc.creator | Jagait, Arshdeep | |
| dc.creator.orcid | 0009-0007-0997-1013 | |
| dc.date.accessioned | 2023-10-03T19:13:28Z | |
| dc.date.available | 2023-10-03T19:13:28Z | |
| dc.date.copyright | 2023 | |
| dc.date.created | 2023-11 | |
| dc.date.issued | 2023-10-03 | |
| dc.date.submitted | November 2023 | |
| dc.date.updated | 2023-10-03T19:13:28Z | |
| dc.description.abstract | Late-onset Alzheimer’s disease (LOAD) is a neurodegenerative condition characterized by a gradual deterioration of the cognitive faculties associated with memory and learning in patients aged 65 or older. Recent advances in the generation of Alzheimer’s disease (AD) mice models have allowed for researchers to better capture such phenomena preclinically in a manner that mirrors the condition in humans. Dietary habits associated with sucrose intake have been identified as a pervasive risk factor in AD pathogenesis. The present study aims to identify if sucrose consumption interacts with the genetic backgrounds of mice to further aggravate this risk as well as its severity. In studying LOAD, mice of both sexes were acquired from various genetic backgrounds: wildtype (WT), humanized amyloid precursor protein (hAPP) or humanized APP/APOE ε4 (hAPP/APOE ε4). At three months of age, mice were randomly assigned to either the control (con) or high-sucrose (hS) water diets until sacrifice (nine months of age). During the fifth month of their dietary regimens, mice were assessed behaviourally for evidence of cognitive decline. The following month, tissues were harvested, and biochemical testing of the cortical samples for AD biomarkers proceeded thereafter. Behavioural testing using the Barnes maze and modified Y-maze indicated that male mice of differing genotypes on the hS diet demonstrated declines in memory in a contextdependent in manner. That is, in either the presence or absence of fear cues. Female hAPP and hAPP/APOE ε4 mice raised on the hS diet, however, only depicted initial impairments in learning on the Barnes maze. Post-mortem spectrophotometric testing was performed to evaluate acetylcholinesterase (AChE) activity indicative of early-stage AD. In the cortical samples of male mice that possess the humanized APP gene, AChE activity was elevated, and especially so for the male mice raised on the hS diet. Together, it can be inferred that AD pathogenesis may follow a genotype-environment interaction. However, further testing is necessary to confirm the hypotheses mentioned herein. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/10388/15096 | |
| dc.language.iso | en | |
| dc.subject | Late-onset Alzheimer's disease | |
| dc.subject | Neurodegeneration | |
| dc.subject | Sugar | |
| dc.subject | APOE ε4 | |
| dc.title | A Model of Sporadic Late-Onset Alzheimer’s Disease in Humanized APP & APOE ε4 Knock-in Mice Raised on a High-Sucrose Diet | |
| dc.type | Thesis | |
| dc.type.material | text | |
| thesis.degree.department | Anatomy, Physiology, and Pharmacology | |
| thesis.degree.discipline | Anatomy, Physiology, and Pharmacology | |
| thesis.degree.grantor | University of Saskatchewan | |
| thesis.degree.level | Masters | |
| thesis.degree.name | Master of Science (M.Sc.) |