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2018 Alzheimer's Association Research Fellowship (AARF)

Determining how genetic diversity of myeloid cells impacts AD progression

How do brain cells that increase inflammation impact progression of Alzheimer’s?

Hongtian Yang
The Jackson Laboratory
Bar Harbor, ME - United States


Recent research suggests that brain inflammation causes nerve cell damage and contributes to the worsening symptoms of Alzheimer’s. Inflammation in the brain is controlled by various types of immune-like cells called myeloid cells, which produce and release factors that either increase or decrease inflammation. Previous studies have tried to identify the types of myeloid cells that contribute to inflammation in Alzheimer’s using mice that develop Alzheimer’s disease-like brain changes. Unlike mice, humans have greater variation in their genes and Alzheimer’s develops differently from individual to individual. For this reason, identifying the myeloid cells involved in brain inflammation will require the study of many different types of model systems that include different sets of genes that contribute to Alzheimer’s-like brain changes.

Research Plan

Dr. Hongtian Yang proposes to identify these myeloid cell types from five different kinds of mice, each genetically-engineered to carry an Alzheimer’s risk gene and to develop Alzheimer’s-like brain changes. The researchers will isolate and examine the types of myeloid cells from these five types of engineered mice and use a sophisticated software technique to identify the genes in these cells that contribute to brain inflammation. Dr. Yang then plans to test the effects of these genes on myeloid cells grown in a laboratory dish. Finally, the researchers will compare the specific mouse genes involved in brain inflammation to genes in cognitively unimpaired individuals and those with Alzheimer’s.


Identification of the myeloid cell types and genes that contribute to inflammation in the brain may lead to new therapeutic approaches that “turn off” or “turn on” these genes in myeloid cells to prevent nerve cell damage and slow the progression of Alzheimer’s.

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