P1‐321: Evidence of Neuroinflammation in the Retina in Presymptomatic Alzheimer's Disease

There is growing literature on potential ocular and/or retinal biomarkers of Alzheimer's disease (AD), ranging from diminished volumes of retinal nerve cell layers and/or the retinal nerve fiber layer to evidence of Aβ deposits in the lens. All studies on retinal markers, thus far, have shown a loss of tissue that appears to increase with disease severity, in studies comparing patients with MCI or AD to healthy controls. The aim of this study is to characterize structural differences in retinal layers and determine whether such differences are associated with visual field impairments in healthy adults at risk for AD, some of whom are likely in the pre-symptomatic stage (based on positive Aβ imaging [SUVR≥1.10). Healthy individuals with high and low cortical Aβ burden (n=32), determined from florbetapir PET imaging, underwent spectral-domain optical coherence tomography. Participants also completed a test of central and peripheral vision using the Heidelberg Edge Perimeter Standard Automated Perimetry (SAP) and Flicker-Defined Form (FDF) stimuli. Compared to those with low Aβ, individuals with high Aβ showed increased volume and thickness of a moderate magnitude in the retinal nerve fiber layer (d ‰ˇ0.35), ganglion cell layer (d ‰ˇ0.55), and inner nuclear layer (d ‰ˇ0.30). Further, increased Aβ burden was significantly associated with worse visual perimetry performance, but only when assessed using the FDF stimuli (r =0.47), and not the SAP stimuli (r =0.06). In the earliest pre-symptomatic stage of AD, inflammatory processes affect retinal nerve cell layers. This inflammatory process, with commensurate volume increases, likely precedes eventual volume decreases with disease progression. Numerous studies have suggested that Aβ-induced inflammation may play a critical and early role in AD pathogenesis, and one study found similar evidence of inflammation in the rat retina following intravitreal administration of Aβ. Impairments in visual fields were also identified with increasing Aβ levels but only when more challenging stimuli (FDF) were used. Taken together, the results provide preliminary but important insights into the early structural and functional retinal changes in preclinical AD.