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2017 Grants - Choi
Targeting Adult Neurogenesis for Alzheimer’s Disease Therapy
Se Hoon Choi, Ph.D.
Massachusetts General Hospital
2017 Alzheimer’s Association Research Grant (AARG)
How might enhancing the brain’s ability to produce new neurons be an effective therapy for Alzheimer’s disease?
Neural stem cells are immature cells that can develop into any kind of brain cell. In healthy brains, they are used to generate new neurons in the hippocampus, a brain region that is vital for learning and memory and is especially vulnerable to Alzheimer’s disease. Recent evidence suggests that this process, known as adult hippocampal neurogenesis (i.e. the ability of the brain to generate new cells in the hippocampal area), becomes impaired during the earliest stages of Alzheimer’s — before the development beta-amyloid plaques, tau tangles and other dementia-related brain changes. This finding suggests that impaired neurogenesis may be a key factor in initiating Alzheimer’s disease. However, scientists remain unclear whether such impairment is a primary event that activates plaque and tangle development, or whether it occurs as a response to those changes.
Se Hoon Choi, Ph.D., and colleagues will use their research grant to address these questions. First, they will use various chemical and genetic engineering methods to produce mice that develop (1) various brain changes of Alzheimer’s disease, including amyloid plaques, and (2) reduced adult hippocampal neurogenesis. They will then assess whether reduced neurogenesis may affect, and possibly promote, the other dementia-related changes. Second, the investigators will engineer Alzheimer’s-like mice that develop high levels of adult hippocampal neurogenesis. These animals will be examined to determine if their dementia can be moderated by enhanced neurogenesis alone or by enhanced neurogenesis combined with physical exercise or anti-amyloid compounds. Lastly, Dr. Choi’s team will use brain cells grown in a dish to screen novel chemicals that can boost adult hippocampal neurogenesis.
The results of Dr. Choi’s effort could shed new light on how brain cell loss begins and progresses in Alzheimer’s disease. These results could also lead to novel pharmacologic methods to stimulate new brain cells that slow or stop the progression of Alzheimer’s, as well as other causes of dementia.