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2005 Grant - Kirkwood
Neurophysiological Analysis of Presenilin Function at the Synapse
Alfredo Kirkwood, Ph.D.
Johns Hopkins University School of Medicine
2005 Investigator-Initiated Research Grant
Neurons send and receive chemical messengers across a tiny gap called a synapse. One part of memory formation appears to be an improved efficiency in the sending and receiving of messages. In Alzheimer's disease, one change in the brain is a dysfunction in synaptic transmission and the eventual breakdown of cell-to-cell communication.
Most cases of familial Alzheimer's disease are caused by mutations in the genes for proteins called presenilins. Understanding the normal and disease-related functions of these proteins is important, therefore, in explaining Alzheimer pathology. Alfredo Kirkwood, Ph.D., and colleagues have observed that in genetically altered mice that stop producing presenilins shortly after birth, there is a change in synaptic function and eventual loss of synapses that is similar to the changes that occur in Alzheimer's disease.
In this investigation, the researchers will study mouse brains in which presenilin activity is shut off in certain cells. This should enable them to examine the role of presenilins in the sending or receiving functions of synaptic transmission. The findings from this work may elucidate key events in Alzheimer's disease pathology and suggest knew therapeutic strategies.