Alzheimer's disease: Recent treatment strategies

Alzheimer Disease (AD) is a neurodegenerative disease characterized by two neuropathological hallmarks: extracellular deposition of amyloid plaques and intracellular neurofibrillary tangles. Current treatment for AD (donepezil, galantamine, rivastigmine and memantine) is only symptomatic and has modest benefits. Thus, the development of drugs with the potential to change the progression of the disease has been a priority. Therapies targeting amyloid β have been the focus for almost 30 years. However, highly promising drugs recently failed to show clinical benefits in phase III trials. Even the positive findings presented by Biogen on Aducanumab are not entirely clear and further data is necessary to confirm its validity. Therefore, researchers are turning their efforts around to tau-targeting therapies, since tau protein appears to be better correlated with the severity of cognitive decline than amyloid β. Currently, most anti-tau agents in clinical trials are immunotherapies and they are in the early stages of clinical research. Four monoclonal antibodies anti-tau (Gosuranemab, Tilavonemab, Semorinemab and Zagotenemab) and one anti-tau vaccine (AADvac1) have reached phase II, so far. In this review, we discuss the potential disease-modifying agents tested in clinical trials and update the information of drugs that are still under clinical evaluation.