Post-mortem assessment of retinal phosphorylated tau and amyloid beta in a cohort of neurodegenerative diseases

© 2022 the Alzheimer's Association.Background: The retina provides an opportunity for development of a screening tool to detect early stages of AD. Studies showing the presence of Aβ and p-tau in AD retina are contradictory, and their characterization in a large, neuropathologically confirmed cohort with different neurodegenerative diseases is scarce. In this study we assessed the presence of different tau isoforms and Aβ (4G8) in the retinas of AD cases, control cases, as well as other neurodegenerative diseases, and correlated these directly to cortical cerebral tau and amyloid pathology loads. Method: Post mortem eyes (N = 62) with both clinical history and post-mortem neuropathological reports available were collected through the Netherlands Brain Bank. Donors included AD, PSP, CBD, FTLD, PD(D), DLB, MSA, ALS, MS and controls, with and without cerebral cortical p-tau. Superior-temporal quadrants were cut in 10 µm sections. Sections were immunostained using antibodies directed against p-tau (AT270, AT100, AT8, pS422) and Aβ (4G8). Linear mixed models were used to analyze between-group differences and the relation between brain and retina. Result: Tau appeared as a diffuse neuritic staining, and in some cases as somatodendritic-like staining and was mainly present in the plexiform layers of the retina. AT8, AT100 and AT270 immunoreactivity showed a predilection in the far periphery. AT8 was generally found in tauopathy cases as opposed to non-tauopathy cases. A strong correlation was found between retinal AT8 and brain cortical tau pathology. 4G8 appeared sporadically as extracellular structures, mainly present in the retinal nerve fiber layer, ganglion cell layer and near blood vessels. 4G8 did not differ between control and disease cases, and no group differences or relation with cortical amyloid load was found. Conclusion: P-tau measured with AT8 in the retina correlates with the presence of tau pathology in cortical brain areas. In contrast, Aβ (4G8) immunoreactivity is sporadically present in the retina, is not specific for AD and does not correlate with cortical amyloid load in a large cross-disease cohort. Our study shows that p-tau detected in the retina by AT8 is a potential biomarker candidate for tauopathies.