Soluble TREM2 drives earliest amyloid‐related p‐tau increase in Alzheimer’s disease but attenuates neurodegeneration in advanced disease

Alzheimer’s disease (AD) is characterized by Aβ and tau accumulation, microglial activation, metabolic brain changes, neurodegeneration, and cognitive decline. Studies found both detrimental and protective effects of microglial activation on AD progression, hence neuroinflammation may be a double‐edged sword in AD, which is critical for clinical trials aiming to modulate microglial activation. Here, we used CSF sTREM2 as a proxy of microglial activation to investigate disease stage‐dependent drivers of microglial activation in AD and its associations with the development of tau, metabolic brain changes, and neurodegeneration.