TY - JOUR
T1 - Serum-derived Immunoglobulins alter Amyloid-ß transport across a blood brain barrier in vitro model
AU - Pötsch, Verena
AU - Bennani-Baiti, Barbara
AU - Neuhaus, Winfried
AU - Muchitsch, Eva Maria
AU - Noe, Christian
N1 - 09.02.2010: Datenanforderung UNIVIS-DATEN-DAT.RA-2 (Import Sachbearbeiter)
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
U2 - 10.1691/ph.2010.9319
DO - 10.1691/ph.2010.9319
M3 - Article
VL - 65
SP - 267
EP - 273
JO - Die Pharmazie: an international journal of pharmaceutical sciences
JF - Die Pharmazie: an international journal of pharmaceutical sciences
SN - 0031-7144
IS - 4
ER -