Amyloid beta deposits in ex vivo retinas correlate with the severity of Alzheimer’s brain pathology.

Abstract

Purpose : Alzheimer’s disease (AD) is a neurodegenerative disease with characteristic deposition of amyloid beta (Aβ) in the brain. The retina, in which Aβ deposits have been detected in vivo, is optically accessible. Here we compare ex vivo Aβ neuropathology of the brain and eye at time of death.

Methods : Eyes and brains were obtained in compliance with the Declaration of Helsinki from healthy subjects and patients diagnosed with AD. One eye was fixed in 4% paraformaldehyde or 10% formalin. The retina was stained with 0.1% Thioflavin-S and counterstained with DAPI, flat mounted in quadrants, and imaged using a Nikon transmission (FITC) microscope, equipped with a polarimeter. Aβ deposits were counted using fluorescence and polarimetry. Quadrants not examined, were assigned a number of Aβ deposits equal to the average number of Aβ deposits in the other quadrants. Brains were examined by a neuropathologist and the severity of AD pathology determined according to NIA guidelines based on assessment of neuritic senile plaque numbers (CERAD), anatomical distribution of Aβ deposits (Thal phase, TP), anatomical distribution of tau-immunoreactive neurofibrillary tangles (Braak stage, BS), and a cumulative score of the severity of AD pathology (CSS). The number of deposits found in the anterior layers of the retina with a signal in both fluorescence and polarimetry were then compared to these measures of AD brain pathology.

Results : There were no Aβ deposits in the retina of the individual whose brain showed no AD pathology. For individuals with a high level of AD brain pathology (n=6), there were more retinal Aβ deposits than in the individual with an intermediate level of AD brain pathology. The Spearman’s rhos (ρ) between number of retinal Aβ deposits and CSS as well as TP of AD brain pathology were significant, but insignificant for CERAD as well as for BS. Gamma (γ) agreed with ρ for CSS and TP (γ=1 strong relationship) and BS (γ=0.33 weak relationship), but not for CERAD (γ=0.76 moderate relationship).

Conclusions : These Aβ deposits in the retina would be large enough to be resolved in vivo. In this initial sample, the number of retinal Aβ deposits correlates both to a cumulative score of AD brain pathology and to a measure of brain amyloid pathology. There was a weak relationship with neurofibrillary tangles. Thus in vivo retinal imaging of Aβ deposits is a promising diagnostic of AD brain pathology.

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