Retinal amyloid beta load in Alzheimer’s disease

Abstract

Purpose : Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by excessive amyloid beta (Aβ) deposition in the brain. Definitive diagnosis of AD is only possible by autopsy. Currently, surrogate tests such as positron emission tomography is used to measure cerebral Aβ burden, but this is expensive and involves radiation exposure. The retina is a neurosensory extension of the central nervous system that can be readily visualized, making it a viable candidate as an accessible AD biomarker tissue complementary to brain imaging. Aβ in the retina has been reported in several AD-transgenic murine models. The purpose of this study is to assess the retinal Aβ load in AD and normal donors.

Methods : Retinal samples from AD and age-matched control donors were processed as free floating punches (3mm) and paraffin embedded cross sections (6um) using mouse monoclonal Aβ antibodies (6F/3D) and Cy3 secondary antibodies. The punches were taken from the fovea, peri-fovea, and 3 peripheral locations (superior, temporal, and inferior). Each punch was imaged on a Zeiss 510 confocal microscope with Zen software. Retinal Aβ load was measured quantitatively in Cy3-stained images by pixel counting.

Results : From the 25 retinal whole mounts (AD n=15, controls n=10), total 117 retinal punches (24 fovea, 21 peri-fovea, 25 superior, 24 temporal, and 23 inferior) were included in the study. Both intra-and extracellular retinal Aβ were assessed. In all donors, foveal and peri-foveal retinal tissue had significantly fewer cells that stained positive for Aβ as compared to the peripheral retina (p<0.0001). These Aβ positive cells were similar in diameter between the various quadrants (p=0.49). AD donors had significantly higher intra- and extracellular Aβ load than controls in all examined regions, except intracellular load in the foveal region and extracellular load in the superior region, which showed no significant difference compared to controls.

Conclusions : High retinal Aβ load was associated with a diagnosis of AD. The results of this study showcase the potential of retinal Aβ imaging as a minimally invasive AD screening method, and highlight the peripheral rather than central retina as an important site for examination in ongoing prospective studies.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.