Retinal phosphorylated tau correlates with the presence of microglia in Alzheimer’s disease and primary tauopathies.

Abstract

AbstractBackgroundPhosphorylated tau (p‐tau) is a hallmark of neurodegenerative diseases such as Alzheimer’s disease (AD). We recently showed that p‐tau in the retina was increased in the plexiform layers of the retina in patients with AD and other tauopathies[1]. Microglia, the resident immune cells of the central nervous system, have also been found to be activated in the retina of patients with AD. To obtain more insight in AD related changes in the retina we investigate the correlation between p‐tau and microglia in the retina of patients with AD and non‐AD tauopathies.MethodRetinal tissue samples were obtained from post‐mortem eyes of patients with AD (n = 16), primary tauopathies (n = 7) and non‐demented controls (n = 11). Immunohistochemistry was performed to detect p‐tau Ser202/Thr205 (AT8) and microglia in activated and resting state (IBA‐1). The mean positive pixel count in the inner plexiform layer (IPL) of p‐tau and microglia were analyzed using Qupath.ResultAs previously described[1], we found increased levels of p‐tau Ser202/Thr205 in controls with Braak NFT I‐III, AD and primary tauopathies. In the current study, p‐tau Ser202/Thr205 was correlated to microglia (IBA‐1). We found a positive correlation between p‐tau Ser202/Thr205 and microglia in the inner plexiform layer of the far (rs[46] = 0.29, p < 0.05) and mid periphery of the retina (rs[42] = 0.37, p < 0.05).ConclusionOur findings show a correlation between the presence of p‐tau Ser202/Thr205 and microglia as assessed with IBA‐1 in a cohort of non‐demented controls, AD cases and non‐AD tauopathies. These results suggest that microglia play role in retinal tau pathology, and support the strong connection between microglia activation and tau pathology as observed in the brain. The results of this study may provide new insights into the pathology of AD in the retina and provide opportunities for early detection and monitoring treatment of the disease.1. Phosphorylated tau in the retina correlates with tau pathology in the brain in Alzheimer’s disease and primary tauopathies. Acta Neuropathol, 2023. 145(2): p. 197‐218 https://doi.org/10.1007/s00401-022-02525-1.