The study of Alzheimer’s Disease (AD) has been hindered by the absence of animal models of late-onset/age-related AD (also termed sporadic AD) (95% of AD cases) since current transgenic mouse models exhibit pathological changes dependent on overexpression of mutant human genes linked to early-onset, familial AD (5% of cases). Oxidative stress is considered to be a causative factor in age-related AD, and we have found that aldehyde dehydrogenase 2 (Aldh2) null mice exhibit not only oxidative stress, but also display many AD-like pathologies. The current study used behavioral analysis to assess whether Aldh2-/- mice also exhibit memory and cognition deficits. Male and female wild type and Aldh2-/- mice were tested monthly beginning at three months of age, using the open field novel object recognition test (a measure of recognition memory), as well as spontaneous alternations in the Y-maze (a measure of spatial working memory). In both tasks, significant decreases in performance occurred in Aldh2-/- mice by 3.5-4 months of age, and this progressively declined over the next three months compared to wild type mice. Sex-related differences in memory impairment were not observed. These results, together with the findings that AD-like pathologies are also present, suggest that Aldh2-/- mice represent a new, oxidative stress-based model of age-related cognitive impairment and AD. This model may prove useful both for assessing AD therapeutics and for gaining better insight into the pathogenesis of AD. / Thesis (Master, Pharmacology & Toxicology) -- Queen's University, 2013-09-26 11:20:00.023
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OKQ.1974/8335 |
| Date | 28 September 2013 |
| Creators | Elharram, AHMED |
| Contributors | Queen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.)) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner. |
| Relation | Canadian theses |
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