Alzheimer’s disease is a progressive neurodegenerative disorder leading to dementia. Interestingly, AD is more prevalent in women than men, where two third of the diagnosed AD population is female. The underlying neuropathology is characterized by extracellular A𝛽 plaques and intracellular tau tangles leading to neuronal cell death. The hippocampus, the main site for learning and memory exhibits the most significant neuronal loss in AD. It is also one of the primary neurogenic niches in the adult brain. A decline of hippocampal neural stem cells is a common feature of AD indicating a defect in neurogenesis. To model AD neuropathology, a triple transgenic model of AD (3xTg) was used. We hypothesize that the defects associated with adult neurogenesis precede the onset of AD hallmarks. Our data showed that neurogenesis defects are present as early as post-natal day 5 of age in the 3xTg model of AD, well before the development of the neuropathology. The early defects were also observed in the TgCRND8 model of AD at 3 months of age. Moreover, no statistically significant difference was detected between male and female mice at 3 months and 9 months of age when investigating NSC populations. This could indicate that sex may not need to be taken in consideration in research design when investigating NSC decline in 3xTg mice. These findings are of clinical relevance, as they may identify early changes that may open opportunities for therapeutic interventions aiming at preventing or delaying neurodegeneration.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/42665 |
| Date | 14 September 2021 |
| Creators | McNicoll, Marie-Michelle |
| Contributors | Slack, Ruth |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
| Rights | Attribution-ShareAlike 4.0 International, http://creativecommons.org/licenses/by-sa/4.0/ |
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