Premium
P3‐483: Intravenous immunoglobulin binds to tau, pTau and PrPc in addition to Aβ
Author(s) -
Schaub Alexander,
Kropf Alain,
Cattepoel Susann,
Ender Miriam,
Bolli Reinhard,
Fabri Louis,
Miescher Sylvia
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1928
Subject(s) - antibody , monoclonal antibody , antigen , chemistry , blocking antibody , immunology , medicine
Background: Intravenous Immunoglobulin (IVIG) is being used in phase III clinical studies to assess its efficacy in mild-to-moderate Alzheimer’s disease (AD) patients. Beside beneficial effects in smaller scale clinical settings, the rationale for using IVIG in AD is based on observations of reduced levels of anti-amyloid beta (Aß)antibodies in AD patients and the presence of these antibodies in normal IVIG preparations (R. Dodel, J Neurol 2004; N Relkin, Neurobiol Aging, 2009). We examined whether Privigen (10% IVIG product) contains specific antibodies that bind to proteins implicated in AD pathology that might explain mechanisms of action in addition to the direct binding of Aß. IVIG is hypothesized to mediate its beneficial effects in chronic inflammatory and autoimmune conditions by a variety of mechanisms. As this might also be the case for AD we measured Privigen binding to Tau, phosphorylated Tau (pTau) and the cellular prion protein (PrP). Methods: The binding of Privigen to antigens was measured by ELISA. Differences in IVIG binding were observed during method development as a result of both antibody and blocking solutions that were used. Results: We show herein that Privigen binds to Aß, as well as tau, ptau and PrP, but not a-synuclein under the same experimental conditions. We also demonstrate that the influence of blocking solutions and antibody diluents on natural auto antibodies is greater than on monoclonal or high titre antibodies. Conclusions: The interaction of Privigen with additional antigens (tau, ptau, PrP) points towards possible mechanisms of action of IVIG in AD that go beyond the direct binding of Aß. Tauhas been the target of immunotherapeutic strategies in the past, where both passive and active immunization improved pathology in neurofibrillary tangle mouse models. Additionally, we have measured binding to PrP, which has been shown to function as a receptor for Aß and can induce neuronal apoptosis upon ligation. The binding of Privigen to these proteins might have beneficial effects by preventing tau-aggregation and PrP-induced cell death. Further experiments will be necessary to address these putative mechanisms of action at a functional level.