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Lysosomes Mediate Rab27b-Dependent Secretion Of Beta-Amyloid, Shany Lahan

Electronic Thesis and Dissertation Repository

Extracellular deposition of beta-Amyloid (Aβ) is an early event in Alzheimer’s disease development. However, it is not known how Aβ is secreted. Lysosomes readily undergo calcium-dependent exocytosis, a process that relies on small GTPase Rab27b. In addition, lysosomal enzymes have been found within extracellular amyloid plaques. We hypothesized that lysosomes mediate Rab27b-dependent exocytosis of Aβ. Neuro-2a cells were transfected with wild-type or mutant Rab27b constructs and/or a lysosomal marker. Cells were incubated with Aβ monomers and imaged using a confocal microscope before and after stimulation of calcium-dependent exocytosis. We observed a significant decrease in lysosome and Aβ co-localization post-treatment in …

Mri Investigations Of Metabolic And Structural Brain Changes In Alzheimer’S Disease And Vitamin D Deprivation, Dickson Wong

Electronic Thesis and Dissertation Repository

Alzheimer's disease (AD) is a neurodegenerative disorder of the brain that presents as progressive impairment across several cognitive domains. The biological mechanisms underlying the development of AD remain unclear, with amyloid-beta plaques, neurofibrillary tangles, calcium dysregulation, and oxidative stress all contributing to neurodegeneration in AD. Vitamin D (VitD) deficiency, a common condition in the elderly, may modulate these mechanisms and complicate the AD process. Due to this complicated pathogenesis, the diagnosis of AD requires subjective clinical judgement, staging of AD is challenging, and it remains difficult to predict when and who will progress to AD. The purpose of this thesis …

'I Honoured Him Until The End': Storytelling Of Indigenous Female Caregivers And Care Providers Focused On Alzheimer's Disease And Other Dementias (Adod), Danielle E. Alcock

Electronic Thesis and Dissertation Repository

Focused on the experiences of Indigenous female caregivers for a loved one diagnosed with Alzheimer’s disease and other dementias (ADOD); this study uses Indigenous methodology of oral storytelling to examine systemic barriers of navigating the Canadian healthcare system. Non-Indigenous healthcare providers who care for families and individuals affected by dementia also share their experiences to give insight to culturally safe care and what institutional supports are needed for frontline staff to achieve this.

Indigenous caregivers were all Anishanaabe and Métis who share stories about caring for their male loved ones. Through their stories of strength and resiliency, the importance of …

Identifying Neuroimaging And Genetic Correlates Of Delusions And Hallucinations In Alzheimer’S Disease, Juweiriya Ahmed

Electronic Thesis and Dissertation Repository

The co-occurrence of psychotic symptoms and Alzheimer’s disease (AD) is a devastating phenotype that affects around 50% of individuals with AD. We hypothesized that distinct interactions between brain structures and genetic variants in dopaminergic, cholinergic and glutamatergic neurotransmitter systems may be associated with the presence of hallucinations and delusions in AD. Using the Alzheimer’s Disease Neuroimaging Initiative, we identified participants that presented with symptoms of delusions, hallucinations, or both symptoms. PLS-CA was used to identify differences in patterns of interactions between 15 single nucleotide polymorphisms and 82 neuroanatomical regions of interest between AD patients endorsing symptoms of delusions, hallucinations, and …