ABSTRACT
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 (Aβ) plaque deposition.
Areas covered: We provide an overview of the molecular pathology that leads to an increase in Aβ peptide accumulation, of the mechanism of action for antibody mediated therapies and of the therapeutic vaccines that target Aβ under development. We also discuss the rationale for using vaccines in the early stages of the disease.
Expert opinion: The major components of β-amyloid plaques are Aβ1-42 and Aβ1-40 peptides derived from the APP. Reducing these plaques by means of passive or active vaccination against Aβ-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.
Trial registration: ClinicalTrials.gov identifier: NCT02565511.
Article highlights
Targeting plaques in progressed patients is too late
Vaccination should essentially be prophylactic
Current vaccines may fail to induce high enough antibody levels
Currently vaccines may target the wrong Aβ-species
Monoclonal antibody studies may suggest that Aβ3-6 represents the optimal species to be targeted
This box summarizes key points contained in the article.
Acknowledgments
We would like to thank Mona Mohsen for artwork and critically reading the manuscript.
Declaration of interest
MF Bachman founded or co-founded and is a shareholder of Saiba GmbH, Hypopet AG, Evax AG, HealVax GmbH and DepVax GmbH. All these companies are involved in the development of VLP-based vaccines. GT Jennings is the CEO/COO of Hypopet AG. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.