LGALS3 and Cognitive impairment: The most important findings from this study are: (1) HCD in TGF mice age-dependently worsened cerebrovascular dysfunction whereas it triggered cognitive deficits irrespective of age; (2) HCD’s main effect in TGF mouse brain corresponded to an inflammatory response of the WM characterized by upregulation of Gal-3-immunopositive microglial cells; (3) In HCD-fed adult TGF mice, SV treatment reduced WM inflammation, enhanced oligogenesis in the SVZ and migration of OPCs in the cc, and fully rescued both cerebrovascular and cognitive deficits without altering blood cholesterol levels.