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2014 Grants - Han
PACAP Deficit and the Pathogenesis of Alzheimer's Disease
Pengcheng Han, Ph.D
Barrow Neurological Institute at St. Joseph Medical Center
2014 New Investigator Research Grant
Neurotrophic growth factors are proteins produced in the brain and used to support brain cell health and survival. Recent research has found that neurotrophic factors tend to become reduced or altered in people at risk of developing Alzheimer’s disease. The loss of neurotrophic factors may contribute to dementia-related brain cell damage and death.
In preliminary studies of brain samples from people who had Alzheimer’s disease, Pengcheng Han, Ph.D., and colleagues found that a neurotrophic factor called pituitary adenylate cyclase-activating polypeptide (PACAP) is abnormally low. Other studies suggest PACAP may inhibit the production of beta-amyloid — a protein fragment that accumulates into amyloid plaques, a hallmark of Alzheimer’s disease. Thus, declines in PACAP levels may be an important biological factor in the development and progression of Alzheimer’s disease.
For their current grant, Dr. Han and colleagues will assess PACAP levels in brain cells from mice engineered to develop Alzheimer’s-like brain changes. They will test whether low PACAP levels may affect the production of beta-amyloid and abnormal tau, another protein thought to play an important role in the development of Alzheimer’s disease. They will also determine links between PACAP loss and the function of synapses — specialized connections between brain cells that are essential for cellular communication and ultimately learning, memory and other cognitive functions. Synaptic damage is a key factor in memory loss for people with Alzheimer’s disease. Collectively, these efforts could shed new light on how the loss of PACAP may affect synaptic loss and subsequent brain changes associated with Alzheimer’s disease. They could also help to identify PACAP-related therapies for preventing or slowing the progression of Alzheimer’s disease.