2008 Grants - Gan

The Role of Microglia in Amyloid Plaque Clearance and Synaptic Pathology

Wen-Biao Gan, Ph.D.
New York University School of Medicine
New York, New York

2008 Investigator-Initiated Research Grant

The protein fragment beta-amyloid tends to accumulate into clumps in the brains of people with Alzheimer's disease. These clumps may be associated with the brain cell damage and memory loss characteristic of Alzheimer's. The presence of beta-amyloid results in the activation of microglia, specialized immune-system cells in the brain. Microglia may help prevent Alzheimer's by "devouring" beta-amyloid and releasing proteins that protect cells and promote cell growth. Yet scientists do not know exactly how microglia target and clear beta-amyloid. Moreover, recent studies have shown that microglia may disrupt cell-to-cell communication in the brain by damaging synapses. Synapses are tiny channels through which brain cells send chemical messages to one another.

Wen-Biao Gan, Ph.D., and colleagues propose to study the role of microglia in both beta-amyloid clearance and in synaptic function. For this effort, they will analyze mice genetically engineered to develop high brain levels of beta-amyloid. The researchers will use a sophisticated imaging technology to determine how microglia in the animals' brains may target and devour beta-amyloid deposits over time. In addition, the researchers will administer a drug to the mice that reduces microglial activation. They will then determine whether this treatment also reduces synapse-related damage near amyloid deposits in the mice brains.

Results of Dr. Gan's study could shed new light on the complex roles microglia play in the brain's communication network. Such work could lead to novel treatments for Alzheimer's disease and other brain disorders.