Dementia Japan 34:13-20, 2020

APOE and TREM2 as key microglial molecules for neurodegenerative phenotypes in Alzheimer’s disease

Tsuneya Ikezu

Departments of Pharmacology & Experimental Therapeutics and Neurology Boston University School of Medicine

Microglia are resident phagocytic cells in the central nervous system and are critical for neuronal damage repair, protein homeostasis, and proteinopathy in aging. In aging and neurodegenerative diseases, characteristic disease-associated microglia are expressed. This is closely related to protein clearance, misfolding, aggregation, synaptic phagocytosis and propagation of misfolded proteins. Proteinopathies and neuronal cell loss in neurodegenerative conditions also contribute to microglial phenotypic changes from homeostatic to disease-associated phenotype, leading to chronic adverse inflammatory responses and further promoting cortical degeneration. This disease-associated microglia-mediated disease mechanism may be a new therapeutic target for AD and related neurodegenerative disorders.

Address correspondence to Dr. Tsuneya Ikezu, Departments of Pharmacology & Experimental Therapeutics and Neurology, Boston University School of Medicine （72 East Concord St, L-606B, Boston, MA 02118, USA）