Amyloid-β Peptide-targeting Immunotherapy in Alzheimer Disease: A Systematic Review of Clinical Studies

Abstract

Background: Amyloid-β (Aβ) peptide accumulation in the brain is a pathological hallmark of Alzheimer disease (AD). Because of the relationship between the Aβ plaque formation and AD progression, targeting Aβ has been advocated as a treatment strategy for this disease. Several studies have focused on immunotherapy methods, such as different vaccination approaches. Materials & Methods: In this systematic review, we explored the main features of the vaccines used to date, including their efficiency in inducing anti-Aβ antibodies and removing Aβ plaques. We also summarized the reported clinical outcomes and mortality rates. A total of 29 articles written in English that describe human clinical trials using three different vaccines (AN1792, CAD106 and AADVac) were reviewed. Results: Based on these studies, most of the patients who received one of these vaccines showed a significant anti-Aβ antibody response at some point during the trial. Several studies reported a decline in Aβ plaque load and an increase in Aβ phagocytosis in different brain regions. The time intervals between the initial vaccination and the booster doses vary among studies, but a 30-day interval has been suggested as the most appropriate by most studies. Meningoencephalitis, microhemorrhages, amyloid encephalopathy, allergic dermatitis and atrial fibrillation have been reported as the most common adverse effects in vaccinated patients. Conclusion: Clinical investigations have shown improved functional and cognitive outcomes, such as the mini-mental state examination score (MMSE), for vaccinated patients compared to the control groups. However, more human clinical studies are needed for a more conclusive evaluation of the properties of different vaccines.

Keywords

• immunotherapy
• alzheimer disease
• amyloid-β peptide
• plaque
• amyloid
• cerebral amyloid angiopathy
• apolipoproteins e