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.
