microglia p1

Can we gain insights into the biology of microglia by studying disease-associated genes?

As the primary defense, immune, and phagocytic cells in the brain, microglia govern multiple aspects of brain development, repair, and aging. In recent years, there has been an increasing appreciation of the contributions of microglia in neurodegenerative, neurodevelopmental, and neuropsychiatric disorders. In particular, the aberrant activation and resolution of microglial responses have been linked to the pathology observed in sporadic or late-onset Alzheimer’s disease. Although genome-wide association studies have revealed a number of genes potentially associated with increased risk of Alzheimer’s disease, and enriched in microglia, large-scale functional analyses of these genes have not been performed to date.

microglia p 2

Are there conserved neuroimmune signatures between pediatric and adult neurodegenerative disorders?

Lysosomal storage disorders (LSDs) result from defects in lysosomal catabolism and frequently present as pediatric neurodegenerative conditions. Mounting evidence suggests that inappropriate activation of innate immune cells actively contributes to the pathology in LSDs, strikingly similar to the reactive microgliosis observed in adult neurodegenerative conditions, such as Alzheimer’s disease. Despite observations indicating that aberrant activation of the immune system is an early event in many LSDs, and treatments such as bone marrow transplants or immunosuppression can be effective for some LSDs, the specific ways in which microglia and macrophages influence the onset or progression of these devastating pediatric diseases have not been thoroughly investigated.