Retinal amyloid beta load is associated with cerebral amyloid angiopathy.

Abstract

Purpose : Alzheimer’s disease (AD) is a neurodegenerative disorder with excessive amyloid beta (Aβ) deposits in the brain. Diagnosis of AD includes positron emission tomography (PET) measure of the brain Aβ; however, PET is expensive and involves radiation exposure. Recent studies have suggested retinal Aβ as a potential biomarker for AD. The purpose of this study is to assess the Aβ load in the retina in AD and normal donors, and test the hypothesis that retinal Aβ load is related to cerebral amyloid angiopathy (CAA).

Methods : Post-mortem brain and retinal tissue from donors with AD (N=11) and non-AD dementia (N=5) and post-mortem retinal tissue from normal, control donors (without dementia) (N=10) were processed. Brain samples were evaluated for neuritic and diffuse senile plaques (CERAD score), Aβ protein (Thal phase), neurofibrillary tangles (Braak stage) and CAA. Retinal samples were processed as free floating punches (4 mm) and paraffin embedded cross sections (6 um) using mouse monoclonal Aβ antibodies (6F/3D) and Cy3 secondary antibodies. Retinal Aβ was measured on Cy3-stained confocal microscopy images by pixel counting.

Results : AD and non-AD dementia donors with no (N = 4) or mild (N=5) CAA were grouped as CAA1, while those with moderate (N = 3) or severe (N = 4) CAA were grouped as CAA2. The group mean retinal Aβ load of normal control, CAA1, and CAA2 were compared using a two-sampled t-test. CAA2 showed significantly greater retinal Aβ load in all regions than normal controls (p < .001) and CAA1 (p = .004). Between CAA1 and normal control group, significant retinal Aβ load difference was observed only in the temporal region (p = .013).

Conclusions : Moderate to high brain CAA levels were associated with high Aβ load in the retina. The results of the study suggest further investigation of the connection between retinal Aβ measurement and brain CAA.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.