Document Type

Article

Publication Date

8-1-2025

Keywords

JMG, SS1, Animals, Methylenetetrahydrofolate Reductase (NADPH2), Disease Models, Animal, Cerebrovascular Disorders, Mice, Retinal Vessels, Male, Female, Brain, Retina, Mice, Transgenic, Electroretinography, Mice, Inbred C57BL

JAX Source

Alzheimers Dement. 2025;21(8):e70501.

ISSN

1552-5279

PMID

40741711

DOI

https://doi.org/10.1002/alz.70501

Abstract

INTRODUCTION: Investigations of retinal biomarkers for Alzheimer's disease (AD) and AD and related dementias (ADRD), has increased significantly. We examine retinal vascular health in a mouse containing the ADRD risk variant Mthfr

METHODS: Morphology and function of retinal vasculature and neurons were assessed using in vivo imaging, immunohistochemistry, and pattern electroretinography. RNAscope and proteomics were employed to determine Mthfr gene expression and differential protein expression in mice carrying Mthfr

RESULTS: Mice show age- and sex-dependent retinal vascular deficits, displaying similarities to previously published brain data. Mthfr is widely expressed and co-localizes with vascular cell markers. Proteomics identified common molecular signatures across the brain and retina.

DISCUSSION: Results demonstrate that Mthfr-dependent vascular phenotypes occur in brain and retina similarly. These data suggest that assessing age and genetic-driven changes within retinal vasculature represents a minimally invasive method to predict AD-related cerebrovascular damage.

HIGHLIGHTS: Mthfr

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