Role of neuroinflammation, microglia, and TREM2 on the progression of amyloid pathology

Keiro Shirotani, Nobuhisa Iwata

Laboratory of Genome-based Drug Discovery Graduate School of Biomedical Sciences Nagasaki University

Neuroinflammation induced by activated microglia is observed in the affected lesions of neurodegenerative disorders including Alzheimer's disease（AD）.　However, precise mechanism how the neuroinflammation contributes to pathogenesis and progression of the disorders remain poorly understood.　Recent genetic studies have identified several AD risk factors are expressed on microglia.　Among them, TREM2（triggering receptor expressed on myeloid cells 2） has the highest odds ratio similar to APOE.　Moreover, accumulated transcriptome studies have found that TREM2 regulates the conversion of homeostatic microglia into disease-associated microglia with two faces, which behave protectively or detrimentally for the disease development.　In this review, we focus on how amyloid pathology is affected by the neuroinflammation, microglia, and TREM2 in Alzheimer's disease models as well as in AD patients.　Therapeutic approaches to modulate a specialized microglial function may provide an opportunity for innovative AD treatments.

Address correspondence to Dr. Keiro Shirotani, Laboratory of Genome-based Drug Discovery Graduate School of Biomedical Sciences Nagasaki University（1-14 Bunkyo-machi, Nagasaki-shi, Nagasaki 852-8521, Japan）