Curcumin, a curry spice ingredient, detects and diff erentiates between pathological tau inclusions in human histological brain sections

Abstract

Background: Curcumin, a natural fl uorochrome and a potent anti-infl ammatory antioxidant used as a spice and as an ayurvedic remedy for centuries, has been shown to label pathologic aggregates of beta amyloid, alphasynuclein and scrapie prion protein, and to reduce their aggregation. Curcumin binding to tau, a protein that pathologically aggregates in a wide family of neurodegenerative diseases, tauopathies, has not been examined, yet. Our study was aimed at assessing curcumin labelling of characteristic pathological deposits of hyperphosphorylated tau protein in brain sections from representative cases of three major classes of tauopathies: Alzheimer’s disease (AD; class 1), progressive supranuclear palsy (PSP; class 2) and Pick’s disease (PiD; class 3). Methods: Th e structures of interest were fi rst identifi ed in HE-stained sections and photographed. Subsequently, the visualization of these structures with curcumin and AT8 immunofl uorescence was assessed by sequential labelling and computer-assisted photography of the same loci. Results were expressed as percentage of structures labelled. Results: Curcumin detected fi brillar tau in AD (95 %) and PSP (90 %), but not in PiD. When comparing curcumin labelling to AT8 immunofl uorescence in AD and PSP, curcumin labelled fi brillar AT8-positive, but not non-fi brillar AT8-immunofl uorescent structures. Curcumin also labelled extracellular fi brillar tangles remaining aft er neuronal death in AD and PSP, which were not visualized by AT8 immunofl uorescence. Conclusions: Curcumin fl uorescence was shown to diff erentiate between pathological tau deposits in two ways. Firstly, it preferentially detected tau deposits with fi brillar morphology. Secondly, curcumin also diff erentiated between representative cases of main tauopathy classes: it did not reveal fi brillar Pick bodies, while clearly labelling neurofi brillar tangles found in AD and PSP.