The eyes -- specifically the outer edges of the retina -- may provide a window into the earliest onset of Alzheimer's disease, long before irreversible damage occurs in the brain.
This is the conclusion of new research from Houston Methodist Hospital's Academic Institute, which point to changes in retinal cells that appear in the very first stages of the disease, potentially opening the door to earlier diagnosis and treatment through routine eye exams.
Historically, most clinical eye exams have concentrated on the central retina, which is responsible for sharp, detailed vision.
However, the Houston Methodist research, led by Dr. Stephen Wong, found that the most critical early indicators of Alzheimer's may be hidden in the peripheral retina. This outer region of the eye contains a higher concentration of Müller glial -- support cells that play a key role in maintaining retinal health.
Using mouse models, the researchers examined how these glial cells change in the earliest stages of the condition that is expected to affect more than 150 million people worldwide by 2050.
The study revealed that these cells undergo significant cellular and structural changes well before other Alzheimer's symptoms appear. These alterations are consistent with patterns seen in people who have been diagnosed with Alzheimer's disease.
A key focus of the research was Aquaporin-4, a protein in the central nervous system that helps flush metabolic waste from the brain, including proteins linked to Alzheimer's disease. The study found that Aquaporin-4 levels increase in the earliest stages of the disease. This increase is associated with stress in the peripheral retina, which shows up as a rise in both the size and number of glial cells.
According to the researchers, this retinal stress is visual evidence that the body is working harder to maintain balance before the system eventually begins to fail in later stages of Alzheimer's disease, as the condition progresses.
In simple terms, the eyes may start showing signs of strain as it tries to compensate for early disease-related changes occurring elsewhere in the body.
The findings also shed light on the eye's role in the glymphatic system, often described as the brain's "plumbing" network, which clears metabolic, brain-specific waste products, such as amyloid-beta and tau proteins, during deep sleep.
By identifying retinal changes that occur before this system breaks down, the research suggests doctors may one day be able to detect Alzheimer's years earlier than is currently possible.
Das, G., Raghunathan, R., Wang,L., Wan,Z., Vasquez,M., Zhao,H., & Wong,S.T. (2026). Retinal Müller glia alterations and their impact on ocular glymphatic clearance in an Alzheimer's disease mouse model. Journal of Alzheimer's Disease. https://doi.org/10.1177/13872877261418165