Grant: Master's Award: Canada Graduate Scholarships

Alzheimer's disease is characterized by the progressive loss of brain cells, namely cholinergic neurons. Cholinergic neurons are a specialized type of neuron that produces the chemical compound acetylcholine and is essential to critical brain functions, including learning and memory. The loss of cholinergic neurons in specific brain areas has been shown to contribute to cognitive deficits in patients with Alzheimer's disease. Molecules that regulate the maintenance, survival and regeneration of cholinergic neurons during brain development and aging, including pathological aging (i.e. Alzheimer's disease) have yet to be fully characterized. Several growth factors are known to promote cholinergic functions, however other families of molecules have also been suspected to regulate cholinergic neurons. My research proposal focuses on the neural cell adhesion molecule (NCAM) and its large sugar component, polysialic acid (PSA). I propose that this cell adhesion molecule is involved in the formation and maintenance of cholinergic neurons. I will test this hypothesis by establishing the role of NCAM and PSA during the development and maintenance of the cholinergic phenotype throughout brain development and aging, and in a mouse model of Alzheimer's disease. I will then investigate whether the administration of NCAM-related therapeutics, that are currently in the early stages of clinical trials for the treatment of neurological disorders, can promote the survival and improve the function of cholinergic neurons. This study will be the first to establish whether the cell adhesion molecule NCAM and its sugar component PSA are critical towards the development and maintenance of cholinergic neurons during normal and pathological aging. The outcomes of this research present potential translational avenues in therapeutic restoration of cognitive deficit, leading to an enhanced quality of life in patients with Alzheimer's disease.