Recent therapeutic strategies targeting beta amyloid and tauopathies in Alzheimer's disease

• Published in: Brain research bulletin Vol. 146; pp. 171 - 184
• Main Authors: Madav, Yamini, Wairkar, Sarika, Prabhakar, Bala
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2019
• Subjects: Alzheimer Disease - pathology; Alzheimer Disease - therapy; Alzheimer’s disease; Amyloid beta; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - physiology; Drug Therapy; Humans; Immunotherapy; Neurofibrillary Tangles - pathology; Pharmacotherapy; Plaque, Amyloid - pathology; Plaque, Amyloid - therapy; Tau proteins; tau Proteins - metabolism; Tauopathies - pathology; Tauopathies - therapy; APP; AD; BBB; Amyloid beta; Alzheimer’s disease; Pharmacotherapy; MAP; NFT; Tau proteins; BACE
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2019.01.004

•Amyloid plaques and neurofibrillary tangles are key features of AD.•Amyloid formation and processing mechanism are targeted for AD therapy.•Inhibiting tau dysfunctioning is another important approach to resolve AD pathology.•Immunotherapy is a promising approach for treating advanced AD. Alzheimer’s disease (AD) has been a global concern for years due to its severe implications that affects the quality of life of the patients. The available line of therapy for treating Alzheimer’s includes acetylcholinesterase inhibitors, NMDA(N-methyl-D-aspartate) antagonists and their combination which gives only symptomatic relief rather than treating the root cause of AD. Senile plaques and neurofibrillary tangles are the characteristic features underlying Alzheimer’s pathology. Several attempts have been made towards exploring the niceties of these hallmarks and targeting various aspects of amyloid and tau pathology at different stages to eliminate the ultimate cause. Approaches targeting cleavage and formation of toxic amyloid fragments by secretases, aggregation of amyloid monofilaments, and immunotherapy against amyloid deposits has been extensively studied to treat amyloid pathology. Similarly, for tau pathology, tau hyperphosphorylation, microtubule stabilization, anti-tau immunotherapy has been explored. This article focuses on AD pathology and current pharmacotherapy, precisely for amyloid and tau. Furthermore, preclinical and clinical studies along with potential leads discovered under these approaches have also been included in this article. However, despite extensive research in drug development, overcoming clinical barrier still remain a major challenge for Alzheimer’s pharmacotherapy.