Alzheimer s disease (AD) is the most widespread dementia syndrome showing progressive presence of abundant deposits of extracellular senile β-amyloid polypeptide (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) consisting of Tau protein.[1, 2] Tau protein is an intrinsically disordered protein that is abundant in neuronal axons where it promotes and stabilizes microtubule assembly.[3] With progression of AD, Tau aggregates and accumulates into NFTs.[2] As there is still no causative treatment or cure for AD and other tauopathies, Tau-based research aims to reveal the pathological consequences of amyloid formation and to implement new therapeutic strategies. In this effort, identification of inhibitors of tau aggregation as potential disease-modifying drugs and investigation of their mode of action play an important role.[4]

Methylene Blue (MB), a tricyclic phenothiazine also known as methylthionine hydrochloride,[5] has a history of diverse medical applications stretching back over 100 years, including use for distinctive cellular targets.[6] MB has been shown to prevent Tau aggregation in vitro [6–8] and to reduce the amount of Tau aggregates in a C. elegans model of Tau pathology.[9] This treatment has relieved Tau-induced toxicity of treated worms.[9] Moreover, MB progressed to phase 2 clinical trials in human AD patients with promising results [10] and was recently announced to enter a phase3 clinical