Retinal Pathology in a Non-Human Primate Model of Late-Onset Alzheimer’s Disease

Abstract

Purpose : Recent evidence in humans and mouse models suggests that the retina exhibits signs of Alzheimer’s Disease (AD) and could serve as a non-invasive diagnostic of AD-associated pathology. We sought to determine whether elderly vervets (African green monkey), at risk for late-onset AD, exhibited retina quantifiable changes in retina phenotypes.

Methods : We examined retina from middle-aged (8-13 years old, N=7) and elderly (25-30 years old, N=6) vervets from the Vervet Research Colony (VRC) of Wake Forest for indicators of retina morphology, neuronal pathology, and gliosis. Changes in retinal lamination and morphology were quantified in toluidine-stained retina sections. To assess neural morphology and gliosis, retina sections were immunohistochemically labeled with neuronal markers (β-Tubulin III, neurofilament light chain (NFLC)) and glial cells (Glial Fibrillary Acidic Protein (GFAP), Iba-1, and glutamine synthetase). Quantitative assessments were performed with FIJI ImageJ. AD status in brain was assessed by the concentration of guanidine-extracted amyloid-beta (Aβ) and quantification of Aβ plaque load.

Results : Elderly vervets exhibited a 45% and 7% increase in total thickness in central and peripheral retina, respectively (p<0.05). These age-dependent changes were attributable to inner retina, which were 96% and 15% thicker in central and peripheral retina, respectively (p<0.05). Outer retina exhibited no age-related changes (p>0.05). Central retina from elderly vervets exhibited increased β-tub staining in RNFL, and NFLC staining in RNFL, IPL, and ONL compared to the middle-aged tissues (p<0.05). Gliotic markers indicated an increase in GFAP in GCL and RNFL and reduced intensity of GS between ONL and RNFL in elderly retina compared to middle-aged retina (p<0.05). Middle-aged brain tissue confirmed the absence of Aβ deposition with no AD probability based on the CERAD Score. Elderly vervets (n=5) exhibited Aβ plaque deposition in the temporal and occipital gyri and were AD ‘probable’, based on the CERAD score.

Conclusions : Our results are the first to characterize age-related changes in the vervet retina with significant changes in retina morphology, neuronal morphology and gliosis that correlate with AD neuropathology in brain. Our findings offer insight on the potential for retina phenotypes to serve as a biomarker of AD in this non-human primate AD model.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.