TREM2 and amyloidosis: Given the strong evidence supporting the role of TREM2 and DAP12 inhibitory TLR signals (Ito and Hamerman, 2012), it is possible to hypothesize that in NHD, amyloid-stimulated TLR activation is disinhibited, with consequent excessive microglial activation and reduced ability to phagocytose amyloid deposits or apoptotic neurons.