Intravenous Immunoglobulins as a Treatment for Alzheimer’s Disease Rationale and Current Evidence Richard Dodel, 1 Frauke Neff, 1 Carmen Noelker, 1 Refik Pul, 2 Yansheng Du, 3 Michael Bacher 1 and Wolfgang Oertel 1 1 Department of Neurology, Philipps-University, Marburg, Germany 2 Department of Neurology, Hannover Medical School, Hannover, Germany 3 Department of Neurology, Indiana University, Indianapolis, Indiana, USA Abstract 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 b-amyloid (Ab) 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 auto- antibodies (nAbs-Ab) that specifically recognize and block the toxic effects of Ab. Furthermore, these nAbs-Ab are reduced in AD patients compared with healthy controls, supporting the notion of replacement with IVIG. Beyond the occurrence of nAbs-Ab, 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. Intravenous immunoglobulin (IVIG) is a fractionated blood product that is used in the treatment of a variety of health conditions. In- itially, its main indication was as a substitution therapy in patients with immune defects such as agammaglobulinaemia or hypogammaglobulin- aemia. Following the treatment of two children with hypogammaglobulinaemia and coincidental idiopathic thrombocytopenic purpura (ITP), an immunomodulatory effect was postulated. Since this observation was made, a large number of diseases with an autoimmune pathophysiology have been treated at least experimentally with IVIG. As early as 1982, IVIG was introduced for the treatment of autoimmune neurological diseases such as multiple sclerosis and shortly after also for the treatment of myasthenia gravis, chronic inflammatory polyneuropathies and Guillain-Barre´ syndrome. [1] Since then, there has been an ever-increasing number of indications in LEADING ARTICLE Drugs 2010; 70 (5): 513-528 0012-6667/10/0005-0513/$55.55/0 ª 2010 Adis Data Information BV. All rights reserved.