The main conclusions from our study are (1) gal3 protein is increased tenfold in human AD brains and is mostly restricted to plaque-associated microglia in humans and 5xFAD mice, (2) certain SNPs linked to the LGALS3 gene are associated with AD, (3) gal3 deficiency reduces Aβ plaque burden and the overall proinflammatory response and plaque size and improves cognitive performance in 5xFAD/Gal3KO mice, (4) gal3 is an endogenous TREM2 ligand, (5) gal3 is released in response to fAβ and (6) gal3 interacts with Aβ, affecting amyloid plaque morphology. The gene discussed is LGALS3; the disease is amyloidosis.