Your Eyes May Reveal Alzheimer's Before Your Memory Fails

Scientists have discovered that changes in the blood vessels of the retina may reflect the same problems that occur in the brain in people at risk for Alzheimer's. This means that, in the future, a simple eye exam could help identify those at risk for developing the disease early, in a less invasive and more accessible way than current methods.

Alzheimer's disease is one of the leading causes of dementia worldwide, and early diagnosis remains a major challenge. Early detection is essential, as it increases the chances of treatment, follow-up, and improved quality of life for patients.

Currently, the most commonly used tests are magnetic resonance imaging and positron emission tomography (PET), which allow observation of brain structure and activity. It is also possible to analyze the fluid surrounding the brain and spinal cord to look for typical signs of the disease.

However, these tests can be expensive, invasive, uncomfortable, and not always available to everyone. Therefore, scientists have been seeking simpler and more accessible alternatives, such as blood tests or retinal scans, to identify early signs of the disease.

The retina, the layer of tissue at the back of the eye responsible for capturing light and sending visual information to the brain, has attracted a lot of attention. This is because the retina is part of the central nervous system, meaning it's a "window" to the brain.

Because the two share similar types of cells and blood vessels, changes in the retina can reflect changes also occurring in the brain. Thus, a simple fundus exam, often performed during routine ophthalmologist appointments, can help detect early signs of Alzheimer's disease and other dementias.

The researchers in this study decided to investigate precisely this: whether changes in the retina could serve as an early warning of vascular changes (in the blood vessels) occurring in the brain.

To do this, they used mice carrying a genetic alteration called Mthfr^677C>T, a common variation linked to an increased risk of Alzheimer's disease, vascular dementia, and even eye problems like glaucoma. About 40% of the population has this genetic variation, which shows how significant it is.

The method used was quite comprehensive. First, the scientists analyzed the eyes of living mice using imaging techniques that allow them to observe blood vessels and retinal structure in detail, without sacrificing the animals.

Next, they performed a test called electroretinography, which measures the electrical response of retinal neurons to light, helping to understand visual function. Next, they collected samples of retinal and brain tissue and applied specific staining techniques to observe the condition of the vessels and nerve cells under a microscope.

Finally, they analyzed the proteins present in both the brain and retina (a process called proteomics) to determine whether the molecular changes were similar in both tissues.

The results were clear. Mice with the genetic variation showed reduced retinal blood vessel density and changes closely resembling problems observed in the brain in previous studies.

Furthermore, protein analysis revealed that the same biological pathways were altered in both the brain and retina, primarily linked to metabolism and cell survival. This means that the changes seen in the eyes closely mirror those occurring in the brain.

The retinas of animals with the Alzheimer's mutation (Mthfr^677C>T) exhibit age- and sex-dependent reduction in vascular density. (A) Fluorescence angiography was used to obtain in vivo images of the retinal vasculature. After fluorescein injection, the retinas were photographed every minute for 6 minutes, and the images used for analysis were obtained at 4 minutes for each animal. Quantification of vascular density shows reduced vascular density in aged female TT mice (B). The number of major branching vessels also decreased with age in female TT mice (C). n = 6/sex/age/genotype.

These findings are important because they suggest that a simple retinal examination may, in the future, help clinicians identify those at risk of developing Alzheimer's disease or other dementias in a much less invasive and more accessible manner than current methods. In other words, the eyes can act as a "mirror" of the brain, revealing early signs of diseases that affect the mind and memory.

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Retinal vascular dysfunction in the Mthfr677C>T mouse model of cerebrovascular disease

Alaina M. Reagan, Michael MacLean, Travis L. Cossette, and Gareth R. Howell

Alzheimer’s & Dementia, Volume 21, Issue 8 August 2025 e70501

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

Abstract: 

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 Mthfr677C>T to determine if changes in retina mirror similar changes in cerebrovasculature. 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 Mthfr677C>T. 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. 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.