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2017 Grants - Das
Microglial Modulation of Neural Activities in Models of Alzheimer's Disease
Melanie Das, Ph.D.
The J. David Gladstone Institutes
San Francisco, California
2017 Alzheimer's Association Research Fellowship (AARF)
How do microglia in the brain affect the connections between nerve cells in Alzheimer's disease?
Microglia are specialized cells in the brain that control immune responses, but they also release molecules that cause inflammation, which contributes to the development of Alzheimer's disease. Microglia are also involved in the process of reducing the number of connections between nerve cells, a process called "synaptic pruning." Because microglia have both positive and negative effects in the brain, treatments that block microglia may not work or may even worsen Alzheimer's disease.
The harmful inflammatory effects of microglia may be activated by changes in the complex network of nerve cells in the brain that occurs during the development of Alzheimer's disease. In turn, abnormal activation of microglia may further damage the nerve cell network in the brain by causing excess synaptic pruning.
Melanie Das, Ph.D., and colleagues propose to examine the connection between microglia activation and changes in the nerve cell network in the brain. They will use various types of mice that have been genetically engineered to develop an Alzheimer's disease-like condition or that have altered microglia activity. They will first measure whether drugs that decrease abnormal activity in the nerve cell network are able to reduce inflammatory molecules and synaptic pruning by microglia. Then, they will determine whether decreasing microglial cell inflammatory molecule production or blocking synaptic pruning by microglia improves nerve cell network activity.
This study may reveal a new relationship between microglia activity and changes in the nerve cell network seen in Alzheimer's disease. The findings could help guide the development of combination therapies that break the vicious cycle of inflammation and loss of connections between nerve cells that contribute to the symptoms and progression of Alzheimer's disease.