Diversity of transcriptomic microglial phenotypes in aging and Alzheimer's disease

The morphological plasticity of microglia has fascinated neuroscientists for 100 years. Attempts to classify functional phenotypes are hampered by similarities between endogenous brain microglia and peripheral myeloid cells that can enter the brain under pathological conditions. Recent advances in single-cell -omic methodologies have led to an explosion of data regarding gene expression in microglia. Herein, we review the diversity of microglial phenotypes in healthy brains, aging, and Alzheimer's disease (AD); identify knowledge gaps in the body of evidence; and suggest areas in which new knowledge would be useful. Data from human samples and mouse models are compared and contrasted. Understanding the molecular complexity of the microglial response repertoire will suggest new avenues for therapeutic treatments in AD.