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

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 Aβ_1-42 and Aβ_1-40 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.

KEYWORDS:

• Virus like particle
• Aβ_1-42 Aβ_3-6
• vaccine
• Alzheimer’s

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 Aβ_3-6 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.

Additional information

Funding

This paper was not funded.