Describing biomarkers for Alzheimer’s disease: Localization of amyloid-β in the retina

Abstract

Purpose : Retinal localization of amyloid-β (Aβ) protein, the pathological hallmark of Alzheimer’s disease (AD), is not well understood. This study aims to describe Aβ localization in the post-mortem human retina from multiple spatial perspectives.

Methods : Post-mortem human retinal tissue from AD donors and age-matched normal donors were processed. Retinal samples were processed as free floating punches (4 mm) or paraffin embedded cross-sections (5 um) using immunochemistry. Confocal microscopy was used to visualize labeling. Representative images are taken for both retinal punches and cross-sectional samples in all experimental groups. In addition, z-stack pictures where taken for the retinal punches and orthogonal views of the z-stacks were generated using ZEISS ZEN Microscope Software.

Results : Retinal Aβ deposits were mainly visualized at the nerve fiber layer, ganglion cell layer, and outer plexiform layer in both cross-sectional preparations and orthogonal view of retinal punches. Compared to normal controls, stronger Aβ immunoreactivtiy in the retinal ganglion cell layer is seen in AD samples. Visually assessing, most Aβ were present at peripheral retina and a larger number of Aβ deposits were present in AD samples. We recognized two patterns of Aβ deposits. These include clustered Aβ inside retinal ganglion cells, which are likely intracellular deposits, and specked Aβ deposits, which are likely extracellular deposits.

Conclusions : We explored the characteristics of Aβ depositions in the human retina. Aβ depositions were found in multiple retinal cell layers and in two distinct patterns. Visual assessment shows a larger amount Aβ deposits in AD eyes compared to normal control eyes. Future directions include characterizing Aβ colocalization with neuronal, astrocytic and microglial profiles in the human retina.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.