Advances in anti-tau therapeutics for alzheimer’s disease: immunotherapy, gene modulation, and combination approaches

Tau protein abnormalities are more detrimental to neurocognitive function and behaviour than amyloid plaque formation in patients affected by Alzheimer’s Disease (AD) - the most common cause of dementia worldwide. Pathologically, tau misfolding, neurofibrillary tangle formation, hyper phosphorylation, and dissociation from microtubules lead to synaptic dysfunction and neuron death. With this understanding, tau is now a major therapeutic target; there is a growing research effort to assess immunotherapy, kinase inhibitors, and tau aggregation inhibitors, and evidence suggests that combination therapies may have synergistic effects. Although there are many challenges remaining, including poor late-stage trial efficacy and limited therapeutic access through the blood-brain barrier, the preliminary results from early preclinical and clinical studies suggest that tau pathology can be reduced and neuronal function improved. Additionally, RNA interference, antisense oligonucleotides, and other gene-based therapies are under investigation. Overall, tau-directed treatments show promise for the treatment of AD, with particular optimism about improvements in delivery systems and combination therapies that will lead to substantial therapeutic benefits and improved quality of life for patients with AD.