AbstractBackgroundThere is increased interest in in vivo labeling of Alzheimer’s disease (AD) pathology in the retina as a non‐invasive diagnostic approach (Jiang, Wang, Li, Cao, & Li, 2016; Koronyo et al., 2017). While the majority of studies focus on the detection of amyloid beta (Aβ) in the retina, the characterization of tau related pathology is scarce. In this study we assessed the presence of different tau isoforms in the retina in AD as well as other neurodegenerative diseases associated with and without tau pathology.MethodPost mortem eyes were collected through the Netherlands Brain Bank from donors with AD (n=6), progressive supranuclear palsy (PSP, n=2), frontotemporal lobar degeneration (FTLD; FUS and TDP43) (n=4), Lewy body disease (LBD, n=2), multiple system atrophy (MSA, n=2), Parkinson’s disease (PD, n=6), and non‐neurodegenerative controls (n=10). Superior‐temporal quadrants were cut in 10 µm sections. Sections were immunostained using primary antibodies directed against total tau (HT7), early tau phosphorylation (AT8), 3R and 4R tau isoforms (RD3/RD4) and late tau phosphorylation (pS422). The frontal cortex was used as a positive control.ResultTotal tau (HT7) was observed in non‐demented control and neurodegenerative cases (Figure 1). The presence of 3‐ and 4‐repeat isoforms of tau varied within the inner plexiform layer (IPL) and outer plexiform layer (OPL) with more 3‐repeat tau in the IPL and more 4‐repeat tau in the OPL. Only AD and PSP cases showed positive immunoreactivity for AT8, which was found differently distributed in the IPL and OPL (Figure 2). Tau phosphorylated at Ser422 was negative in all groups.ConclusionIn control and neurodegenerative cases, high levels of tau are present in the retina, mainly in the plexiform layers. Interestingly, we found different intensities for 3‐ and 4‐repeat tau in the IPL and OPL, implicating differences in tau expression by amacrine and horizontal cells (Chidlow, Wood, Manavis, Finnie, & Casson, 2017). Tau phosphorylated at Ser202/Thr205 clearly differentiates tauopathies from other neurodegenerative disease and non‐demented controls. Depending on the epitope, phosphorylated tau is a potential retinal biomarker for AD and other tauopathies.