Microglial Tau and Calcium Dysregulation in Alzheimer's Disease

Abstract: Microglia during Alzheimer’s disease (AD) and other neurodegenerative disorders undergo disease-specific changes that may contribute to disease progression. As the brain's immune cells, microglia are the cell type predominantly involved in phagocytosing protein aggregates such as tau. However, microglia clearly fail to eliminate pathological aggregates such as tau, allowing them to persist and AD to progress. A reduction in microglial phagocytic capacity, combined with a pro-inflammatory phenotype, may create a brain environment permissive to tau tangle formation and spread. Intracellular calcium (Ca2+) is known to orchestrate multiple microglial functions, including phagocytosis, proliferation, migration, cytokine production and release, metabolism, and formation of reactive oxygen species, all of which are dysregulated in microglia during AD. Thus, microglia calcium channels may represent an important therapeutic target for the treatment and prevention of AD. This seminar will discuss current research on microglial tau and calcium dysregulation as they relate to AD and other neurodegenerative diseases, and outline future directions examining the intersection of these two aspects of pathology in AD.