In this review, recently published by Wilbur M. Song and Marco Colonna on Nature immunology, the authors gathered the most recent discoveries regarding the transcriptomic, phenotypical, morphological and functional modifications that microglia undergo during different neurodegenerative pathologies. These disease-associated microglia (DAM) are found in different neurodegenerative contests (e.g. Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis) as well as more-neuroinflammatory paradigms (e.g. multiple sclerosis), although their signature (expression of transcription factors and surface markers) may differ significantly, while spanning throughout the vast host of proteins that are expressed both by M1- and M2-like phenotypes. Particular attention has been dedicated to the role of TREM2 receptor and type I/II interferon signaling axes in the induction of DAM phenotype.