Tau-based therapeutics for Alzheimer's disease: active and passive immunotherapy.

Pharmacological manipulation of tau protein in Alzheimer's disease included microtubule-stabilizing agents, tau protein kinase inhibitors, tau aggregation inhibitors, active and passive immunotherapies and, more recently, inhibitors of tau acetylation. Animal studies have shown that both active and passive approaches can remove tau pathology and, in some cases, improve cognitive function. Two active vaccines targeting either nonphosphorylated (AAD-vac1) and phosphorylated tau (ACI-35) have entered Phase I testing. Notwithstanding, the recent discontinuation of the monoclonal antibody RG7345 for Alzheimer's disease, two other antitau antibodies, BMS-986168 and C2N-8E12, are also currently in Phase I testing for progressive supranuclear palsy. After the recent impressive results in animal studies obtained by salsalate, the dimer of salicylic acid, inhibitors of tau acetylation are being actively pursued.