Tau, a microtubule associated protein, stabilizes and maintains microtubule structure and function. Modifications in tau, therefore, can affect its interaction with microtubules leading to its dissociation and aggregation. In the brain of patients with Alzheimer's disease (AD) tau has been found as abnormal aggregates called neurofibrillary tangles (NFTs) and has been considered as a hallmark of the disease. NFTs are composed of complex paired helical filaments (PHF) of hyperphosphorylated tau. Tau aggregation coupled with beta-amyloid deposition in brain has been observed in association with neuronal degeneration leading to memory loss and impaired cognitive functions.

An aqueous extract of cinnamon (Cinnamomum zeylanicum), a commonly used spice, was found to have the ability to inhibit tau aggregation in vitro and even bring about partial disassembly of already aggregated tau (PHF) obtained from AD patients.

In the present study, we investigated the effect of two compounds, cinnamaldehyde (CA) and Epicatechin (EC), active components of cinnamon extract, on tau aggregation in vitro and their ability to protect hippocampal neurons from oxidative stress induced cellular damage, a major cause implicated in the pathogenesis of AD. It was found that CA and EC can completely inhibit tau aggregation in vitro. The interaction was found to occur between these compounds and the thiol groups of the two cysteine residues of tau, importantly, in a reversible manner. Further, CA and EC could protect tau from reactive oxygen species mediated oxidation and prevent subsequent formation of high molecular weight species. CA and EC were found to protect primary rat hippocampal neurons in culture from oxidative stress induced disintegration and death. Furthermore, impairment of insulin sensitivity and reduced glucose uptake in neuronal cells due to oxidative stress were restored to normal levels following treatment with CA and EC.