Alzheimer’s Disease Drug Discovery and Development Consortium: Modulating CD33 Function and Neuroinflammation as a Therapeutic Approach for Alzheimer’s Disease

2021, 2022

The innate immune receptor CD33 inhibits brain amyloid beta clearance and promotes neuroinflammation in Alzheimer’s disease. CD33 is a very interesting target for developing therapeutics for the prevention and treatment of Alzheimer’s disease. We identified two CD33-specific antibodies that downregulated CD33 protein levels in microglia. These antibodies will be evaluated for their ability to inhibit CD33 activity in microglial cells. Through an unbiased high-throughput screen of a natural product library, we identified natural products that reduced levels of pro-inflammatory mediators in microglia. Several combinations of natural products showed additive effects in reducing levels of pro-inflammatory mediators in microglia. Furthermore, we are currently screening an FDA-approved drug library for modulation of amyloid beta uptake in microglia. Hits from the primary screen will be validated in dose-dependent amyloid beta uptake assays in microglia. These studies are expected to facilitate Alzheimer’s disease therapeutics based on modulation of neuroinflammation.


Funding to Date



Drug Discovery, Drug Screening Projects


Ana Griciuc, Ph.D.