Alzheimer's disease (AD) and other neurodegenerative diseases are a major cause of death and disability for older Americans, with a US prevalence of more than 6.5 million. As AD currently cannot be cured or prevented, there is an urgent need for effective treatments targeting underlying disease processes. A major roadblock in treatment development has been the lack of good targets. Although pathologically important, amyloid beta plaques and tau tangles are not easily druggable, and clinical trials of therapeutics targeting these proteins directly have largely failed. Recent genome-wide association studies have identified a link between a growing number of modulatory proteins on neuroimmune cells, particularly on the surface of microglia and astrocytes, that are linked to the risk of developing AD. The identification of new proteins with neuroimmunomodulatory activities could enable an entirely new generation of therapeutic targets with the potential to treat, delay, and possibly even prevent AD and other neurodegenerative diseases.
The human health significance of the proposed work is the identification of new targets on neuroimmune cells for treating Alzheimer's disease (AD) and other neurodegenerative diseases. Currently, no drug on the market targets the underlying disease process of AD, and therapeutics against traditional targets in AD have repeatedly failed in late-stage clinical trials. These factors highlight an urgent need to identify new therapeutic targets in AD. Most importantly, these new targets should be relevant in the early, asymptomatic stages of disease where intervention can slow, stop, or prevent disease progression. Neuroimmune cell modulators offer this potential.
