Intravenous immunoglobulins as a treatment for Alzheimer's disease: rationale and current evidence

Current treatment options for Alzheimer's disease (AD) exert only a short-lived effect on disease symptoms. Active and passive immunotherapy have both been shown to be effective in clearing plaques, removing beta-amyloid (Abeta) and improving behaviour in animal models of AD. Although the first active immunization trial in humans was discontinued because of severe adverse effects, several new approaches are currently being investigated in clinical trials. Recently, commercially available intravenous immunoglobulins (IVIG) have been used in small pilot trials for the treatment of patients with AD, based on the hypothesis that IVIG contains naturally occurring autoantibodies (nAbs-Abeta) that specifically recognize and block the toxic effects of Abeta. Furthermore, these nAbs-Abeta are reduced in AD patients compared with healthy controls, supporting the notion of replacement with IVIG. Beyond the occurrence of nAbs-Abeta, evidence for several other mechanisms associated with IVIG in AD has been reported in preclinical experiments and clinical studies. In 2009, a phase III clinical trial involving more than 360 AD patients was initiated and may provide conclusive evidence for the effect of IVIG as a treatment option for AD in 2011. In this article, we review the current knowledge and scientific rationale for using IVIG in patients with AD and other neurodegenerative disorders.