Tolfenamic Acid: A Modifier of the Tau Protein and its Role in Cognition and Tauopathy

Abstract

Background: Tangles are deposits of hyperphosphorylated tau, which are found in multiple neurodegenerative disorders that are referred to as tauopathies, of which Alzheimer's disease (AD) is the most common. Tauopathies are clinically characterized by dementia and share common cortical lesions composed of aggregates of the protein tau.

Objective: In this study, we explored the therapeutic potential of tolfenamic acid (TA), in modifying disease processes in a transgenic animal model that carries the human tau gene (hTau).

Methods: Behavioral tests, Western blotting and Immunohistochemical analysis were used to demonstrate the efficacy of TA.

Results: Treatment of TA improved improving spatial learning deficits and memory impairments in young and aged hTau mice. Western blot analysis of the hTau protein revealed reductions in total tau as well as in sitespecific hyperphosphorylation of tau in response to TA administration. Immunohistochemical analysis for phosphorylated tau protein revealed reduced staining in the frontal cortex, hippocampus, and striatum in animals treated with TA.

Conclusion: TA holds the potential as a disease-modifying agent for the treatment of tauopathies including AD.

Keywords: Alzheimer's disease; dementia; hTau mouse model; microtubule-associated protein Tau (MAPT); tauopathy; tolfenamic acid..