Variants in the triggering receptor expressed on myeloid cells 2 ( TREM2) gene are linked with an increased risk of dementia, in particular the R47H het TREM2 variant is linked to late-onset Alzheimer’s disease. Using human iPSC-derived microglia, we assessed whether variations in the dynamics of exosome secretion, including their components, from these cells might underlie some of this risk. We found exosome size was not altered between common variant controls and R47H het variants, but the amount and constitution of exosomes secreted were different. Exosome quantities were rescued by incubation with an ATP donor or with lipids via a phosphatidylserine TREM2 ligand. Following a lipopolysaccharide or phagocytic cell stimulus, exosomes Abbreviations used : AD = Alzheimer’s disease, CPZ = chlorpromazine, Cv = common variant, CytoD = Cytochalasin D, DIV = days in vitro, EB = embryoid bodies, ER = endoplasmic reticulum, FACs = fluorescence activated cell sorting, H 2 O 2 = hydrogen peroxide, iPSC = induced pluripotent stem cells, iPS-Mg = induced pluripotent stem cell-derived microglia, LC-MS = liquid chromatography mass spectrometry, LPS = lipopolysaccharide, NTA = nanoparticle tracking analysis, PBST = phosphate buffered saline solution with 1% TWEEN-20, PI = propidium iodide, PS + = phosphatidylserine, RA = retinoic acid, SDC = sodium deoxycholate, SN = supernatant, TREM2 = triggering receptor expressed on myeloid cells 2. ppm; Da; modifications: phosphorylation.