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

2021

The microglial regulator CD33 modulates brain amyloid beta clearance and neuroinflammation in Alzheimer’s disease. Through an unbiased high-throughput screen of a natural product library, we identified natural products that reduced levels of pro-inflammatory mediators in microglia. We also independently identified several FDA-approved drugs that increased amyloid beta uptake and reduced inflammation in a microglial cell line stably expressing human CD33. Here, we will screen an FDA-approved drug library for modulation of amyloid beta uptake and clearance in microglial cells. We will investigate whether the hits from the primary screen increase amyloid-beta uptake and reduce levels of pro-inflammatory mediators using dose-dependent assays in microglia. To identify CD33 inhibitors, we will screen novel CD33-specific antibodies for modulation in microglia of CD33 levels, amyloid beta uptake and inflammation. These studies should greatly facilitate novel therapeutic approaches for Alzheimer’s disease based on targeting CD33 and neuroinflammation.

 


Funding to Date

$197,500

Focus

Drug Discovery, Drug Screening Projects

Researchers

Ana Griciuc, Ph.D.