title: Passive anti-amyloid immunotherapy in Alzheimer's disease: What are the most promising targets?
abstract: Alzheimer's disease (AD) is the most common dementia in the industrialized world, with prevalence rates well over 30% in the over 80-years-old population. The dementia causes enormous costs to the social healthcare systems, as well as personal tragedies for the patients, families and caregivers. AD is strongly associated with Amyloid-beta (Aβ) protein aggregation, which results in extracellular plaques in the brain, and according to the amyloid cascade hypothesis appeared to be a promising target for the development of AD therapeutics. Within the past decade convincing data has arisen positioning the soluble prefibrillar Aβ-aggregates as the prime toxic agents in AD. However, different Aβ aggregate species are described but their remarkable metastability hampers the identification of a target species for immunization. Passive immunotherapy with monoclonal antibodies (mAbs) against Aβ is in late clinical development but recently the two most advanced mAbs, Bapineuzumab and Solanezumab, targeting an N-terminal or central epitope, respectively, failed to meet their target of improving or stabilizing cognition and function. Preliminary data from off-label treatment of a small cohort for 3 years with intravenous polyclonal immunoglobulins (IVIG) that appear to target different conformational epitopes indicate a cognitive stabilization. Thus, it might be the more promising strategy reducing the whole spectrum of Aβ-aggregates than to focus on a single aggregate species for immunization.
authors.affiliation: Institute of Applied Biotechnology, Faculty for Biotechnology, Biberach University of Applied Science, Karlstrasse 11, Biberach/Riss, D-88400, Germany. zimmermann@hochschule-bc.de.
authors.forename: Jens
authors.initials: J
authors.lastname: Moreth
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Mavoungou
authors.forename: Katharina
authors.initials: K
authors.lastname: Schindowski