TREM2 and amyloidosis: In a normalized state, neuronal apoE4 promotes tau phosphorylation and cell death by modulating microglial activation, however, impaired apoE4 dysregulates homeostatic microglial functioning playing a role in amyloid plaque degradation due to its reduced affinity to TREM2 (triggering receptor expressed on myeloid cells 2) receptors expressed by microglial cells [104].