Identifying New Immunomodulatory Targets for Alzheimers and Other Neurodegenerative Diseases

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ABSTRACT 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.