Alzheimer’s disease (AD) remains a major public health challenge, affecting over 50 million individuals globally. While traditionally characterized by amyloid-beta plaques and neurofibrillary tangles, increasing evidence highlights the critical role of neuroinflammation and microglial dysfunction in AD pathogenesis. Microglia—the resident immune cells of the central nervous system—are highly dynamic responders to injury, infection, and degeneration. Among key molecular regulators, the triggering receptor expressed on myeloid cells 2 (TREM2) has emerged as a significant genetic risk factor for AD. TREM2 mutations can increase AD susceptibility by impairing ligand binding or downstream signaling, thus diminishing microglial responses to pathological stimuli.1–3
Studying TREM2 signaling in primary microglial cells is limited by scarce availability and phenotypic instability in vitro. The development of human induced pluripotent stem cell (iPSC)-derived microglia overcomes these limitations by providing renewable, disease-relevant models that recapitulate primary microglial features.
In this study, we utilized iCell® Microglia from FUJIFILM Cellular Dynamics to investigate TREM2- dependent signaling. The Leo™ and Jess™ Systems, powered by capillary-based immunoassay Simple Western™ Technology were employed to enable highly sensitive, multiplexed, and quantitative analysis of post-translational modifications and total protein levels. Highly-validated rabbit monoclonal antibodies from Cell Signaling Technology® (CST) were used to assess microglial responses, focusing on Syk and PLCγ2 phosphorylation as downstream readouts of TREM2 activation.
