Previous research has suggested that changes in the eye’s blood vessels could reflect vascular dysfunction in the brain, one of the earliest biological changes linked to ADRD. In this case, retinal vascular changes could serve as biomarkers for identifying individuals at risk of Alzheimer’s and related dementias. It was found that mice carrying the Mthfr677C>T genetic variant displayed age- and sex-dependent changes in retinal blood vessels. Together, these results suggest that changes in the retina’s blood vessels reflect underlying problems in the brain’s blood vessels caused by Mthfr677C>T, and they may serve as early indicators of Alzheimer’s disease and related dementias. Fluorescein angiography also detected trends that didn’t reach statistical significance, and widespread Mthfr expression prevented identification of specific cell types driving the vascular changes.