The retina is a potential source of biomarkers for the detection of neurodegenerative disease.Accumulation of phosphorylated tau (p-tau) in the brain is a pathological feature characteristic for Alzheimer's disease (AD) and primary tauopathies. In this study the presence of p-tau in the retina in relation to tau pathology in the brain was assessed. Post-mortem eyes and brains were collected through the Netherlands Brain Bank from donors with AD (n=17), primary tauopathies (n=8), αsynucleinopathies (n=13), other neurodegenerative diseases including non-tau frontotemporal lobar degeneration (FTLD) (n=9), and controls (n=15). Retina cross-sections were assessed by immunohistochemistry using antibodies directed against total tau (HT7), 3R and 4R tau isoforms (RD3, RD4), and phospho-epitopes Ser202/Thr205 (AT8), Thr217 (anti-T217), Thr212/Ser214 (AT100), Thr181 (AT270), Ser396 (anti-pS396) and Ser422 (anti-pS422). Retinal tau load was compared to p-tau Ser202/Thr205 and p-tau Thr217 load in various brain regions. Total tau, 3R and 4R tau isoforms were most prominently present in the inner plexiform layer (IPL) and outer plexiform layer ( OPL) of the retina and were detected in all cases and controls as a diffuse and somatodendritic signal.Total tau, p-tau Ser202/Thr205 and p-tau Thr217 was observed in amacrine and horizontal cells of the inner nuclear layer (INL). Various antibodies directed against phospho-epitopes of tau showed immunoreactivity in the IPL, OPL, and INL. P-tau Ser202/Thr205 and Thr217 showed significant discrimination between AD and other tauopathies, and non-tauopathy cases including controls. Whilst immunopositivity was observed for p-tau Thr212/Ser214, Thr181 and Ser396, there were no group differences. P-tau Ser422 did not show any immunoreactivity in the retina. The presence of retinal p-tau Ser202/Thr205 and Thr217 correlated with Braak stage for NFTs and with the presence of p-tau Ser202/Thr205 in hippocampus and cortical brain regions. Depending on the phospho-epitope, p-tau in the retina is a potential biomarker for AD and primary tauopathies.

Introduction Previous work has showed the in vivo presence of retinal amyloid in Alzheimer's disease (AD) patients using curcumin. We aimed to replicate these findings in an amyloid biomarker–confirmed cohort. Methods Twenty‐six patients with AD (age 66 [+9], Mini‐Mental Status Examination [MMSE] ≥17) and 14 controls (age 71 [+12]) used one of three curcumin formulations: Longvida, Theracurmin, and Novasol. Plasma levels were determined and pre‐ and post‐curcumin retinal fluorescence scans were assessed visually in all cases and quantitatively assessed in a subset. Results Visual assessment showed no difference between AD patients and controls for pre‐ and post‐curcumin images. This was confirmed by quantitative analyses on a subset. Mean conjugated plasma curcumin levels were 198.7 nM (Longvida), 576.6 nM (Theracurmin), and 1605.8 nM (Novasol). Discussion We found no difference in retinal fluorescence between amyloid‐confirmed AD cases and control participants, using Longvida and two additional curcumin formulations. Additional replication studies in amyloid‐confirmed cohorts are needed to assess the diagnostic value of retinal fluorescence as an AD biomarker.

INTRODUCTION: Previous work showed in-vivo presence of retinal amyloid in AD patients using curcumin. We aimed to replicate these findings in an amyloid biomarker confirmed cohort. METHODS: Twenty-six AD patients (age 66 (+9), MMSE>17) and 14 controls (age 71(+12)) used three curcumin formulations: Longvida, Theracurmin and Novasol. Plasma levels were determined and pre- and post- curcumin retinal scans acquired using autofluorescence imaging. Images were both visually and quantitatively assessed. RESULTS: Visual assessment showed no difference between AD patients and controls for pre-and post-curcumin images. This was confirmed by quantitative analyses. Mean plasma curcumin levels were 198.7 nM (Longvida), 576.6 nM (Theracurmin) and 1605.8 nM (Novasol). DISCUSSION: We found no difference in retinal focal fluorescence in an amyloid biomarker confirmed cohort of AD patients and controls, using Longvida (previously used for this purpose) and two additional curcumin formulations yielding higher curcumin plasma levels. We therefore question the presence of retinal amyloid.