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INCREASED PRESENCE OF PHOSPHORYLATED TAU IN THE RETINA OF ALZHEIMER’S DISEASE AND OTHER TAUOPATHIES
There is increased interest in in vivo labeling of Alzheimer’s disease (AD) pathology in the retina as a non-invasive, low-cost diagnostic approach. In this study we assessed the presence of different tau isoforms in post-mortem retinas of AD and controls, as well as other neurodegenerative diseases associated with or without tau pathology.
Post-mortem eyes were collected through the Netherlands Brain Bank from donors with AD (n=17), frontotemporal lobar degeneration (FTLD; n=6), other tauopathies (n=7), alpha-synucleinopathies (n=13), as well as non-neurodegenerative controls (n=16) and other neurodegenerative cases (n=3). Cross-sections of the superior-temporal quadrants were immunostained for total tau (HT7), early tau phosphorylation (AT8, AT100, AT270), 3R and 4R tau isoforms (RD3/RD4) and late tau phosphorylation (pS422).
Total tau (HT-7) was observed in all cases. 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. In general, AD and other tauopathy cases showed positive immunoreactivity for AT8. Tau phosphorylated at Ser422 was negative in all groups.
In controls with cerebral cortical tau and neurodegenerative tauopathy cases, high levels of tau are present in the retina, mainly in the plexiform layers. Overall, tau phosphorylated at Ser202/Thr205 differentiates tauopathies from other neurodegenerative diseases and non-neurodegenerative controls. Depending on the epitope, phosphorylated tau is a potential retinal biomarker for AD and other tauopathies.