Could retinal changes help predict Alzheimer’s disease onset?

Alzheimer’s disease (AD) is a degenerative condition that affects the brain due to the accumulation of protein aggregates, mainly amyloid β (Aβ) and tau protein. The most accepted hypothesis is that these aggregates compromise the synapses between neurons, causing neurological symptoms such as memory loss, disorientation, and cognitive decline.1

Although significant progress has been made in the diagnosis of AD, differentiating AD from other causes of dementia remains challenging. Currently, AD diagnosis relies on a thorough history, cognitive tests, blood sample analysis, and brain image scans.2 In vivo biomarkers of AD are also available in clinical trials and some clinical practice.3

To improve and accelerate the diagnosis of AD, researchers are looking at retinal tissues to identify early signs of disease onset before clinical symptoms appear. Some changes in the retina have been associated with AD development, such as neuron loss, visual impairment, retinal thinning, and nerve fibers reduction.4 These retinal alterations are grouped and categorized as Alzheimer’s retinopathy, a field of research in rapid progression.5 

Recently, new retinal alterations were reported in Acta Neuropathologica regarding capillary loss and deficiency of platelet-derived growth factor receptor beta (PDGFRβ). This study analyzed postmortem retinal tissues from 56 human donors and used specific imaging and quantification techniques to detect changes in the tissue.6 Researchers found a substantial accumulation of the isoform Aβ40 in the retina of patients with mild cognitive impairment (MCI) and AD compared to cognitively normal individuals (p < 0.001). This accumulation was associated with PDGFRβ loss (r=− 0.66, p=0.00001), compromising vascular integrity in the retina. Additionally, the researchers observed significant pericyte degeneration in AD compared to controls (p < 0.05). Furthermore, correlations between retinal vascular abnormalities, such as retinal PDGFRβ loss, and cerebral Aβ burden were identified in subjects with neuropathological reports (n=20).6

In a second study published in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, the same group showed a correlation between increased retinal amyloid plaques in the proximal mid‐periphery (PMP) of the supero-temporal quadrant and decreased hippocampal volume (r=−0.41, p=0.03). Compared to cognitively normal individuals, patients with MCI and AD showed a significant increase in amyloid accumulation in the PMP, with a large effect size (p=0.042, Cohen d=0.83).7

In an interview with VJDementia, Maya Koronyo-Hamaoui, PhD, Cedars-Sinai Medical Center, Los Angeles, CA, explains how changes in the retina, particularly vascular changes, can help predict, detect and monitor AD. Dr Koronyo-Hamaoui commented that “those vascular changes in the retina predict changes in the brain of patients both in terms of pathology but also in terms of cognitive status”.

Although the retina imaging techniques used in these studies are still experimental and need validation to be used in the clinic, they hold great promise in the field. Overall, these findings open the possibility to use changes in the retina to explore early diagnostic approaches and target therapies in AD.

Written by Luiza Erthal

Edited by Marta Palhas


1. Long, J. M. & Holtzman, D. M. Alzheimer Disease: An Update on Pathobiology and Treatment Strategies. Cell 179, 312–339 (2019).

2. Hane, F. T. et al. Recent Progress in Alzheimer’s Disease Research, Part 3: Diagnosis and Treatment. J. Alzheimers Dis. 57, 645–665 (2017).

3. Snyder, P. J. et al. Retinal imaging in Alzheimer’s and neurodegenerative diseases. Alzheimers Dement. 17, 103–111 (2021).

4. Colligris, P., Perez de Lara, M. J., Colligris, B. & Pintor, J. Ocular Manifestations of Alzheimer’s and Other Neurodegenerative Diseases: The Prospect of the Eye as a Tool for the Early Diagnosis of Alzheimer’s Disease. J. Ophthalmol. 2018, (2018).

5. Mirzaei, N. et al. Alzheimer’s Retinopathy: Seeing Disease in the Eyes. Front. Neurosci. 14, 921 (2020).

6. Shi, H. et al. Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina. Acta Neuropathol. (Berl.) 139, 813–836 (2020).

7. Dumitrascu, O. M. et al. Sectoral segmentation of retinal amyloid imaging in subjects with cognitive decline. Alzheimers Dement. Diagn. Assess. Dis. Monit. 12, (2020).