PMID- 24517534
OWN - NLM
STAT- MEDLINE
DCOM- 20140828
LR  - 20140620
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 130
IP  - 1
DP  - 2014 Jul
TI  - Amyloid-beta concentration and structure influences the transport and 
      immunomodulatory effects of IVIG.
PG  - 136-44
LID - 10.1111/jnc.12678 [doi]
AB  - Intravenous immunoglobulin (IVIG) contains anti-amyloid-beta antibodies as well as 
      antibodies providing immunomodulatory effects that may modify chronic 
      inflammation in Alzheimer's disease. Answers to important questions about IVIG 
      transport into the central nervous system and assessments of any impact amyloid-beta 
      has on this transport can be provided by in vitro models of the blood-brain 
      barrier. In this study, amyloid-beta[1-42] was pre-aggregated into fibrillar or 
      oligomeric structures, and various concentrations were incubated in the brain 
      side of the blood-brain barrier model, followed by IVIG administration in the 
      blood side at the therapeutically relevant concentrations of 5 and 20 mg/mL. IVIG 
      accumulated in the brain side at physiologically relevant levels, with amyloid-beta 
      pre-incubation increasing IVIG accumulation. The increased transport effect was 
      dependent on amyloid-beta structural form, amyloid-beta concentration, and IVIG dose. 
      IVIG was found to decrease monocyte chemotactic protein-1 levels 6.5-18% when low 
      amyloid-beta levels were present and increase levels 4.2-23% when high amyloid-beta 
      levels were present. Therefore, the presence, concentration, and structure of 
      amyloid-beta plays an important role in the effect of IVIG therapy in the brain. The 
      mechanisms of action and transport across the blood-brain barrier (BBB) for an 
      Alzheimer's disease therapeutic, intravenous immunoglobulin (IVIG), remain 
      unknown. We investigated the transport of IVIG across endothelial cell BBB 
      monolayers pre-incubated with amyloid-beta peptides. We found that the concentration 
      and structure of amyloid-beta plays an important role in the effect of IVIG on BBB 
      tightening and cytokine neutralization. (Note: Figure not drawn to scale.).
CI  - (c) 2014 International Society for Neurochemistry.
FAU - Wuest, Diane M
AU  - Wuest DM
AD  - Department of Chemical and Biomolecular Engineering and Delaware Biotechnology 
      Institute, University of Delaware, Newark, Delaware, USA.
FAU - Lee, Kelvin H
AU  - Lee KH
LA  - eng
PT  - Journal Article
DEP - 20140306
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Immunologic Factors)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
SB  - IM
MH  - Amyloid beta-Peptides/*chemistry/*metabolism
MH  - Animals
MH  - Animals, Newborn
MH  - Biological Transport/drug effects/physiology
MH  - Blood-Brain Barrier/metabolism
MH  - Cells, Cultured
MH  - Endothelium, Vascular/chemistry/metabolism
MH  - Immunoglobulins, Intravenous/*metabolism/physiology
MH  - Immunologic Factors/administration & dosage/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Peptide Fragments/*chemistry/*metabolism
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - amyloid-beta
OT  - blood-brain barrier
OT  - in vitro blood-brain barrier model
OT  - inflammation
OT  - intravenous immunoglobulin
EDAT- 2014/02/13 06:00
MHDA- 2014/08/29 06:00
CRDT- 2014/02/13 06:00
PHST- 2013/08/29 00:00 [received]
PHST- 2014/01/25 00:00 [revised]
PHST- 2014/01/28 00:00 [accepted]
PHST- 2014/02/13 06:00 [entrez]
PHST- 2014/02/13 06:00 [pubmed]
PHST- 2014/08/29 06:00 [medline]
AID - 10.1111/jnc.12678 [doi]
PST - ppublish
SO  - J Neurochem. 2014 Jul;130(1):136-44. doi: 10.1111/jnc.12678. Epub 2014 Mar 6.