Biomarkers that were once hidden from physicians’ view may hold the key to early Alzheimer’s disease diagnoses, according to two studies presented at the American Academy of Ophthalmology annual meeting last week.

One study presented at the Chicago conference looked at optical coherence tomography angiography (OCT-A)—a non-invasive technique that can reveal the retinal microvasculature. It showed that changes to this structure are associated with Alzheimer’s development. Specifically, Alzheimer’s patients are known to have reduced vessel density and perfusion density compared with patients with mild cognitive impairment. The idea is that the changes to the retinal microvasculature mirror the small-vessel cerebrovascular changes seen in the brains of Alzheimer’s patients.

Using the imaging technology, researchers found patients who had Alzheimer’s had significantly decreased 3mm circle vessel density (VD) and 3mm ring VD as well as decreased 3mm circle perfusion density (PD) and 3mm ring PD. They also displayed reduced 6mm circle VD as well as significantly decreased inferior ganglion cell-inner plexiform layer (GC-IPL) and inferonasal GC-IPL thicknesses.

The mechanism underlying reduced retinal vessel density in Alzheimer’s patients is unknown, according to the researchers, but one proposal includes decreased angiogenesis from sequestration of vascular endothelial growth factor (VEGF) in amyloid-β (Aβ) plaques and competitive binding of Aβ to VEGF receptor 2.

According to the North Carolina-based research team, Aβ deposition around vascular walls disrupts the basement membrane of small vessels, causing endothelial damage and reducing the vascular lumen. Earlier studies have found Aβ plaques in the retinas of Alzheimer’s patients postmortem, they note.

A second study also connected the disease to retinal changes. That research shows the inner layer of the retina is thinner in people with a family history of Alzheimer’s. Brain scans of those patients also showed a reduction in their hippocampal volume, another tell-tale sign of early Alzheimer’s.

Both studies could provide an opportunity for many more patients to be easily and non-invasively screened for early signs of the condition.