Alzheimer’s disease (AD) is ranked as the third-most expensive illness and sixth
leading cause of mortality. It is associated with the deposition of extracellular
amyloid- (A) in neural plaques (NPs), as well as intracellular
hyperphosphorylated tau proteins that form neurofibrillary tangles (NFTs). As a
new target in regulating neuroinflammation in AD, triggering receptor expressed
on myeloid cells 2 (TREM2) is highly and exclusively expressed on the microglial
surface. TREM2 interacts with adaptor protein DAP12 to initiate signal pathways
that mainly dominant microglia phenotype and phagocytosis mobility. Furthermore,
TREM2 gene mutations confer increased AD risk, and TREM2 deficiency
exhibits more dendritic spine loss around neural plaques. Mechanisms for
regulating TREM2 to alleviate AD has evolved as an area of AD research in recent
years. Current medications targeting A or tau proteins are unable to
reverse AD progression. Emerging evidence implicating neuroinflammation may
provide novel insights, as early microglia-related inflammation can be induced
decades prior to the commencement of AD-related cognitive damage. Physical
exercise can exert a neuroprotective effect over the course of AD progression.
This review aims to (1) summarize the pathogenesis of AD and recent updates in
the field, (2) assess the concept that AD cognitive impairment is closely
correlated with microglia-related inflammation, and (3) review TREM2 functions
and its role between exercise and AD, which is likely to be an
ideal candidate target.