Amyloid beta (Aβ) immunoreactivity in the retina of Alzheimer’s disease (AD) and non-AD dementias: A pilot study

Abstract

Purpose : AD is a devastating neurodegenerative disorder in which Aβ accumulates in the brain beyond normal limits. Assessing Aβ levels in the brain by PET imaging can confirm the presence and progression of AD, however PET imaging is costly and exposes patients to significant radiation. Retinal imaging may be a viable alternative to PET for detection of Aβ in the brain as some studies suggest that Aβ accumulates in AD retina. The purpose of this study is to assess the relationship of Aβ accumulation in the retina and brain of AD donors.

Methods : Autopsy materials from donors with a primary pathological diagnosis of AD were studied to determine the relationship of retinal and brain Aβ loads. Retina and brain of non-AD dementias (cerebral vascular disease, dementia with Lewy bodies), and retina of age-matched normals were processed for controls. Brain samples were evaluated for neuritic and diffuse senile plaques (CERAD score), Aβ protein (Thal phase), neurofibrillary tangles (Braak stage) and cerebral amyloid angiopathy. Retinal samples were processed as free floating punches (4 mm) or paraffin embedded cross sections (6µm) using mouse monoclonal Ab antibodies (6F/3D, 4G8, 6E10) and Cy3 secondary antibodies. Images were captured on a Zeiss 510 confocal microscope with LSM510 or Zen 2009 software. We analyzed labeling in the ganglion cell layer (GCL) and in the nerve fiber layer (NFL) within the central retina as well as peripheral retina (superior, inferior and temporal regions) using NIH Image J.

Results : To date, we have collected eye and brain samples from 15 donors with primary pathological diagnosis of AD and 8 donors with non-AD dementias. Pilot data from N=3 AD and N=3 non-AD dementia donors will be presented. Higher levels of Aβ were observed in the peripheral (temporal) retina compared to central retina in all 6 eyes. The Aβ immunolabeling was present in the blood vessel lumen, the neuropil, and the cytoplasm of cells in the GCL. The relationship of retinal Aβ immunoreactivity and pathological staging of AD will be discussed.

Conclusions : Aβ immunolabeling is evident in the NFL and GCL in human retina. Aβ load is higher in peripheral compared to central retina in both AD and non-AD specimens. Future studies of AD autopsy material as well as mouse models of AD will help define the relationship between the temporal and pathological deposition of Aβ protein in the brain and retina.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.