Anti-amyloid- βAntibodies and Anti-tau Therapies for Alzheimer's Disease: Recent Advances and Perspectives

Amyloid- fi (A fi ) plaques and neurofibrillary tangles containing phosphorylated tau protein are major hallmarks of Alzheimer's disease (AD). Drug discovery efforts to target A fi and tau have been the primary focus for several decades. Recently, substantial breakthroughs have been achieved in the clinical development of A fi antibodies; aducanumab was approved under conditional accelerated pathway by Food and Drug Administration (FDA) in the U.S. as the first disease-modifying agent for treating AD, and lecanemab has been granted traditional full approved in the U.S. and Japan. In addition, donanemab met the primary endpoint in a phase 3 study. On the other hand, tau-targeting therapies have failed to show clinical benefit although that increased tau levels show a strong correlation with cognitive impairment relative to A fi depositions. Currently, tau immunotherapies, such as anti -tau antibodies and tau vaccines, have shown functional benefits in clinical trials. Also, clinical trials for combination therapy of A fi and tau antibodies to see their potential are being investigated. In this review, we provide updates on the results of clinical trials of anti-A fi antibodies and anti -tau therapeutics and suggest future directions for these therapeutics.