MAPT and Brain atrophy: Although TREM2 loss of function mutations could also contribute to neurodegeneration independently of Aβ by impairment of brain energy metabolism [33], synapse dynamics [26, 48], and formation of neurofibrillary tangles [45], a recent study suggests an important role of Aβ pathology in the TREM2 dependent formation of tau pathology and brain atrophy [43].