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2011 Grants - Wiltgen
The Role of Synaptic Plasticity in the Development of Alzheimer's Disease
Brian Wiltgen, Ph.D.
The Regents of the University of California, University of California
Office of Research/Sponsored Programs
2011 New Investigator Research Grant
One of the most vulnerable brain regions in early Alzheimer's disease is the hippocampus, a region important for learning and memory. However, scientists do not completely understand the mechanisms responsible for this vulnerability. According to one theory, brain structures in the hippocampus have different characteristics than they do elsewhere in the brain. For example, the hippocampal synapses — the specialized regions through which brain cells communicate — have much higher plasticity than do synapses in other brain regions. Synaptic plasticity is a mechanism by which the strength of synaptic signals changes. This mechanism probably facilitates learning and memory in the brain. Yet increased plasticity may also make hippocampal neurons more vulnerable to damage from the toxic protein clumps characteristic of Alzheimer's disease. These clumps include plaques of the protein fragment beta-amyloid and neurofibrillary tangles of abnormal tau protein.
For their study, Brian Wiltgen, Ph.D., and colleagues will test this hypothesis using a novel mouse model of Alzheimer's. This animal has been engineered to develop all the major pathologies or brain changes of human dementia amyloid plaques, neurofibrillary tangles and brain cell degeneration. The researchers will crossbreed some of these animals with those of another mouse model that lacks cellular structures linked to synaptic plasticity in the hippocampus. Dr. Wiltgen's team predicts that the mice with less hippocampal plasticity will suffer less disease-related pathology than will the mice with normal plasticity. If this prediction is correct, then the study's findings could shed new light on biological mechanisms of early Alzheimer's.