Our work adds to this body of literature by interrogating the function of TREM2 as a parent trait variable rather than an indicator which varies as a function of pathological state, providing in vivo evidence into how dysfunction in TREM2 enters the AD cascade, working to exacerbate tau spread from the EC into the neocortex likely through aberrant microglial function. The gene discussed is TREM2; the disease is Alzheimer disease.