Prospective Therapies for Alzheimer Disease: Biomarkers, Clinical Trials and Preclinical Research

Most of the 46.8 million people estimated in the year 2015 as living with dementia worldwide were attributed to have Alzheimer’s disease (AD), with projections set to be almost tripled by 2050. Current drugs to treat AD are focused on ameliorating symptoms instead of treating its underlying causes, becoming only palliative. Consequently, treatments to prevent, stop or reverse this overwhelming disease are desperately needful. This Chapter takes a tour through clinical and preclinical studies from different approaches, ranging from those based on small molecules to immunotherapy. But first it also addresses the role of biomarkers in early diagnosis, which is necessary not only to properly recruit patients but also for an accurate assessment of efficiency and safety in clinical trials. Among other approaches, Aβ- immunotherapy has emerged as a promising tool for the treatment of AD. Whereas active immunotherapy, namely administering fragments of the Aβ-peptide, is currently in Phase II, passive immunotherapy, specifically administering antibodies against the Aβ-peptide, reached Phase III. Some of these Phase III trials failed probably because they were performed in patients with mild-to-moderate AD, a too advanced stage of the disease. Currently, different cohorts have been recruited for clinical trials: asymptomatic and very-mildly symptomatic carriers of autosomal-dominant AD mutations as well as symptomatic elderly patients with amyloid positive PET. More studies are needed, but we are getting closer to find a disease-modifying drug to cure this devastating disease.