Regulation of Microglia Phenotypes in Alzheimer’s Disease

The goal of our project is to define transcription factors that drive microglial phenotypes associated with plaques, neurofibrillary tangles, and neurodegeneration in Alzheimer’s disease.

Alzheimer’s disease is defined by the accumulation of harmful proteins in the brain. Microglia, the immune cells of the brain, play a key role in this process, but the molecular mechanisms that lead to distinct phenotypes are unclear. This study will use advanced techniques to isolate and analyze microglia, revealing how they contribute to disease and identifying new targets for developing effective treatments. We will test the hypothesis that specific groups of protein families (MiT/TFE and AP-1), are responsible for controlling the genes that microglia turn on or off in Alzheimer’s disease.

By combining multi-omic approaches (ATAC-seq, ChIP-seq, RNA-seq), we can nominate transcription factor candidates that drive gene expression of microglia associated with Alzheimer’s disease pathology. We can then directly test their impact on microglia function and potentially shift microglia into a beneficial phenotype.

At the end of the study, we will have identified transcription factors implicated in driving altered microglia gene expression in Alzheimer’s disease. We will also have a better understanding of the interplay between microglia phenotypes and Alzheimer’s disease pathology. This knowledge will ultimately lead to new treatment avenues targeting neuroinflammation in Alzheimer’s disease.