A new Alzheimer’s & Dementia study has explored the role the common genetic mutation Mthfr677C>T plays in retinal vascular health, providing evidence that the retina may serve as a minimally invasive biomarker for Alzheimer’s disease (AD) and related dementias (ADRD).
The researchers, based at The Jackson Laboratory (JAX) in Maine, investigated whether retinal vascular dysfunction parallels cerebrovascular changes previously observed in mice carrying the Mthfr677C>T polymorphism, a variant found in up to 40% of the global population.
Using a knock-in mouse model, the team assessed retinal morphology, vascular function, and neuronal integrity through in vivo imaging, fluorescein angiography, OCT, electroretinography, and proteomics. As early as six months of age, they found that retinas from these mice displayed less vessel branching, narrow and swollen arteries, and twisted vessels. By 12 months, female homozygous mice showed significant reductions in retinal vascular density and branching, along with vascular simplification.
These observed retinal changes reflect similar alterations to what happens to the brain in the cognitive decline associated with AD. The findings underscore the retina’s potential as a surrogate marker of cerebrovascular pathology, and, given the accessibility of retinal imaging in clinical practice, reinforce the opportunity for ophthalmologists to contribute to dementia risk stratification and monitoring. Retinal vascular assessment – potentially integrated with AI-driven image analysis – could become a frontline tool in identifying patients at risk for ADRD, particularly in those carrying the MTHFR variant.
