In more advanced stages of the disease, TREM2-expressing microglia, interacting with accumulating neurofibrillary tangles, cause extensive inflammation and neurodegeneration [190,191], but the absence of TREM2 in microglia at this stage of AD, but not at earlier stages, exacerbates AD symptomatology [192,193]. This evidence concerns the gene TREM2 and Alzheimer disease.