Anti-Tau Trials for Alzheimer's Disease: A Report from the EU/US/CTAD Task Force

Efforts to develop effective disease-modifying treatments for Alzheimer's disease (AD) have mostly targeted the amyloid β (Aβ) protein; however, there has recently been increased interest in other targets including phosphorylated tau and other forms of tau. Aggregated tau appears to spread in a characteristic pattern throughout the brain and is thought to drive neurodegeneration. Both neuropathological and imaging studies indicate that tau first appears in the entorhinal cortex and then spreads to the neocortex. Anti-tau therapies currently in Phase 1 or 2 trials include passive and active immunotherapies designed to prevent aggregation, seeding, and spreading, as well as small molecules that modulate tau metabolism and function. EU/US/CTAD Task Force members support advancing the development of anti-tau therapies, which will require novel imaging agents and biomarkers, a deeper understanding of tau biology and the dynamic interaction of tau and Aβ protein, and development of multiple targets and candidate agents addressing the tauopathy of AD. Incorporating tau biomarkers in AD clinical trials will provide additional knowledge about the potential to treat AD by targeting tau.