2024/06/30 by Naoyuki Suzuki, Takuya Hatta, T. Hatta +3
Computer Science · Medicine · #Alzheimer's disease research and treatments #Cholinesterase and Neurodegenerative Diseases #Computational Drug Discovery Methods
paper · pdf · doi:10.1248/cpb.c24-00069
openalex publication_date 2024/06/30 · crossref created 2024/06/30 · crossref issued 2024/07/01 · crossref published 2024/07/01 · crossref published-print 2024/07/01 · crossref deposited 2024/12/21 · openalex created_date 2025/10/10 · crossref indexed 2026/07/31 · openalex updated_date 2026/07/31
Amyloid-β (Aβ) plaques and neurofibrillary tangles containing phosphorylated tau protein are major hallmarks of Alzheimer's disease (AD). Drug discovery efforts to target Aβ and tau have been the primary focus for several decades. Recently, substantial breakthroughs have been achieved in the clinical development of Aβ 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 Aβ 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 Aβ and tau antibodies to see their potential are being investigated. In this review, we provide updates on the results of clinical trials of anti-Aβ antibodies and anti-tau therapeutics and suggest future directions for these therapeutics.