Modulating CD33 Function and Neuroinflammation as a Therapeutic Approach for Alzheimer’s Disease

One of the regulators of amyloid beta clearance in Alzheimer’s disease is a microglial receptor called CD33. Through an unbiased high-throughput screen of a natural product library, we identified natural products that increase amyloid beta uptake and clearance. We also identified FDA-approved medications that increase amyloid beta uptake and maintain microglia in an anti-inflammatory state in the brain. Here, we will screen the natural product library for modulation of levels of pro-inflammatory mediators in microglia. We also will investigate the effects of FDA-approved medications on amyloid beta uptake and inflammation in a microglial cell line stably expressing human CD33. To assess the impact of the most promising hits on tau clearance, we will set up a tau uptake assay in microglia. The development of effective anti-inflammatory medications and CD33 inhibitors should facilitate Alzheimer’s disease therapeutics targeting neuroinflammation.