Serum-derived Immunoglobulins alter Amyloid-ß transport across a blood brain barrier in vitro model

Verena Pötsch, Barbara Bennani-Baiti, Winfried Neuhaus, Eva Maria Muchitsch, Christian Noe (Corresponding author)

    Publications: Contribution to journalArticlePeer Reviewed

    Abstract

    Since passive immunization with serum-derived immunoglobulins (intravenous immunoglobulins) showed several positive effects in some patients with Alzheimer's disease (AD), intravenous immunoglobulins (IVIG) are discussed as a possible treatment option. IVIG, an antibody product derived from human plasma, contains natural antibodies against amyloid beta(A beta) peptide. Until now it is not known, how IVIG interferes with pathogenesis in AD, but several proposed mechanisms are in discussion. Receptor types which are involved in transport processes at the BBB are LRP, RAGE and hFcRn. We were looking for an in vitro BBB model expressing these receptors and studied the alteration of transport of A beta peptides across this model under the influence of immunoglobulins. Cell line ECV304 was found to be suitable for our experiments. We found evidence for involvement of an improved clearance of A beta across the BBB as well as a decreased A beta influx from blood to the brain probably following complex formation of immunoglobulins with free A beta in the periphery. Furthermore, we were able to confirm the activity of IVIG preparations which acted the same way but showed slightly less efficacy in comparison to monoclonal anti-A beta antibodies. Based on these results we suggest multiple mechanisms responsible for the efficacy of immunotherapy in Alzheimer's disease.
    Original languageEnglish
    Pages (from-to)267-273
    Number of pages7
    JournalDie Pharmazie: an international journal of pharmaceutical sciences
    Volume65
    Issue number4
    DOIs
    Publication statusPublished - 2010

    Austrian Fields of Science 2012

    • 3012 Pharmacy, Pharmacology, Toxicology

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