A vaccine against Alzheimer's disease: anything left but faith?

Introduction: Alzheimer's disease looms as a profound and growing threat to future human health. The disease is thought to be primarily driven by aberrant proteolysis of the amyloid precursor protein (APP) and amyloid beta (A beta) plaque deposition. Areas covered: We provide an overview of the molecular pathology that leads to an increase in A beta peptide accumulation, of the mechanism of action for antibody mediated therapies and of the therapeutic vaccines that target A beta under development. We also discuss the rationale for using vaccines in the early stages of the disease. Expert opinion: The major components of beta-amyloid plaques are A beta(1-42) and A beta(1-40) peptides derived from the APP. Reducing these plaques by means of passive or active vaccination against A beta-peptides has been a long-running endeavor but with disappointing results as the impact on disease progression has been minimal. The data gathered to date could suggest that antibodies do not work, mainly because the studies have not been performed in an optimal fashion. The emerging views are that patients should be treated earlier, ideally in the prodromal or symptom free stage, antibody levels have to be high and the correct epitope must be targeted. More clinical trials to fully explore the potential of vaccines are therefore warranted.