Serum-derived immunoglobulins alter amyloid beta transport across a blood-brain barrier in vitro model.
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(Abeta) 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 Abeta 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 Abeta across the BBB as well as a decreased Abeta influx from blood to the brain probably following complex formation of immunoglobulins with free Abeta 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-Abeta antibodies. Based on these results we suggest multiple mechanisms responsible for the efficacy of immunotherapy in Alzheimer's disease.
Poetsch
V
V
Department of Medicinal Chemistry, University of Vienna, Vienna, Austria.
Bennani-Baiti
B
B
Neuhaus
W
W
Muchitsch
E M
EM
Noe
C R
CR
D000465:Algorithms; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007106:Immune Sera / Q000737:chemistry; D007136:Immunoglobulins / Q000097:blood* / Q000494:pharmacology*; D010539:Permeability; D051381:Rats; D011961:Receptors, Fc / Q000187:drug effects
D016229:Amyloid beta-Peptides; D017127:Glycation End Products, Advanced; D007106:Immune Sera; D007136:Immunoglobulins; D011961:Receptors, Fc