Serum-derived immunoglobulins neutralize adverse effects of amyloid-beta peptide on the integrity of a blood-brain barrier in vitro model.
A disrupted blood-brain barrier (BBB) might have major effects on the progression of Alzheimer's disease (AD). This supports the theory of blood as a chronic source of exogenous amyloid-beta (Abeta) peptide as well as other neurotoxic substances in the brain, which would normally be excluded by an intact BBB. In addition to Abeta, neuroinflammation is suggested to contribute to the pathological conditions in AD and is a known disruptor of BBB integrity. Consequently, new therapeutic approaches to stabilize the BBB should be developed. Serum derived immunoglobulins, also called intravenous immunoglobulins (IVIG), are gained from plasma of healthy individuals and were found to induce positive effects in some patients with AD, but mechanisms of action are unclear by now. Moreover, there are no data on how IVIG affects the BBB itself. Therefore, we examined the potency of Abeta peptides as well as neuroinflammatory mediators (TNF-alpha and LPS) either alone or after simultaneous application of IVIG to disintegrate the BBB by evaluating the transport rate of carboxyfluorescein, a marker of paracellular leakage. Our results showed beneficial effects of IVIG on a disrupted BBB, which could positively influence diseases outcome in AD. With a stabilized BBB the brain is prevented from systemic Abeta entry, as well as from entry of other toxic substances from the blood.
Poetsch
Verena
V
Department of Medicinal Chemistry, University of Vienna, Vienna, Austria.
Neuhaus
Winfried
W
Noe
Christian Roland
CR
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005452:Fluoresceins / Q000378:metabolism; D005470:Fluorometry / Q000379:methods; D005910:Glioma / Q000473:pathology; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D016895:Culture Media, Serum-Free; D005452:Fluoresceins; D016756:Immunoglobulins, Intravenous; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C024098:6-carboxyfluorescein