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.