Amyloid-beta and phosphorylated tau in post-mortem Alzheimer's disease retinas

In-vivo labeling of retinal amyloid-beta(A) and tau has potential as non-invasive biomarker for Alzheimer's disease (AD). However, literature on the presence of A and phosphorylated tau (pTau) in AD retinas is inconclusive. We therefore assessed the presence of A and pTau in post-mortem retinas in 6AD and 6 control cases who donated brains and eyes to the Netherlands Brain Bank. Neuropathological diagnosis of AD was made according to NIA-AA criteria. Formalin fixed retinas were dissected in quadrants and cross-sections of medial and superior retinas were made. Immuno-histochemical stainings were performed for A, amyloid precursor protein (APP) and pTau. To assess translation to an in-vivo set up using curcumin as labelling fluorophore, co-stainings with curcumin were performed. No typical A-plaques and neurofibrillary tangles, like in the cerebral cortex, were observed in AD retinas. A diffuse immunoreactive signal for pTau was increased in the inner and outer plexiform layers of the retina in AD cases compared to control cases with absence of cerebral amyloid pathology. Immunostaining with anti-A and anti-APP antibodies yielded signal in ganglion cells, amacrine cells, horizontal cells and Muller cells in both control and AD cases. We observed small extracellular deposits positive for anti-A antibodies 12F4 and 6E10 and negative for 4G8 and curcumin. A subset of these deposits could be characterized as corpora amylacea. In conclusion we found that retinal manifestations of AD pathology appear to be different compared to cerebral AD pathology. Using a qualitative cross-sectional approach, we did not find A/APP related differences in the retina between AD and control subjects. In contrast, tau related changes were found to be present in cases with cerebral AD pathology, suggesting retinal tau as a potential biomarker for AD.