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Testing therapeutic approaches to improve cognitive dysfunction in a primate model of Alzheimer’s Disease

Principal Investigator:
  • Douglas Munoz, Queen's University
Team Members:
  • Stephen Scott, Queen's University
  • Douglas Cook, Queen's University
  • Ron Levy, Queen's University
  • Queen's University

Project Overview

Alzheimer’s Disease (AD) is a severe dementia that is likely a result of years of buildup in the brain of molecules called amyloid-beta oligomers (AβOs). The pursuit of new disease-modifying therapeutics for AD that change the natural progression of AD early in its course is under intense investigation. A major impediment, however, lies in the difficulty of translating therapies that work in animals (usually rodents) to the specific human disease condition. Thus, the main goal of this proposal is to investigate how injection of AβOs in the non-human primate (NHP) brain leads to changes in brain function, expression of early biomarkers of disease, and eventually brain pathology as well as changes in behaviour and cognition. We injected AβOs into the lateral ventricles of adult macaque monkeys and found that this can trigger a pathology in neurons that mimics several attributes of AD. The second main goal of this proposal is to explore two novel neurosurgical approaches that are designed to promote rescue of nerve cells and their connections by implanting trophic molecules and using deep brain stimulation to promote regrowth and plasticity to overcome the damage induced by the AβOs. Thus, the primary goal of this grant is to first establish and track in vivo the impact of AβOs in the NHP brain and determine if they trigger pathological features that resemble the hallmarks of AD. Secondly, we will examine therapeutic strategies to promote regrowth and plasticity. The expected outcome of the proposed studies is the identification of a strategy that could ultimately have profound effects by slowing AD progression and interrupting the onset of AD.