Investigating outcomes of senescence on microglial physiological and immune functions: implications for viral infection and Alzheimer's disease

 

Alzheimer’s disease (AD) is the most prevalent chronic non-communicable disease affecting the central nervous system. It predominantly involves neurodegeneration and cognitive decline associated with progressive memory loss. Epidemiological data have linked an increased risk of AD and dementia with viral infections, including the herpes simplex virus, but the underlying mechanisms remain largely elusive.

Microglia, which are the immune cells of the central nervous system, have recently emerged as critical for maintaining central nervous system health and determining pathological outcomes across various conditions including viral infection, aging, and AD. Several dysfunctional microglial states increased in AD are associated with cellular interruption of its division cycle (senescence). This is an irreversible differentiation process leading to resistance to cell death, which results in decreased neuroprotection and exacerbated inflammation. This project aims to investigate microglial functional diversity in response to viral infection and Alzheimer's disease along the aging trajectory using pre-clinical and animal models.

This project was selected for funding during the first research competition of the Joint Canada-Israel Health Research Program – Phase II. The program is a partnership between IDRC, the Canadian Institutes of Health Research, the Israel Science Foundation and the Azrieli Foundation.