Linked Life Data

15478192

Source:http://linkedlifedata.com/resource/pubmed/id/15478192

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-11-30
pubmed:abstractText
We have previously shown that anti beta-amyloid (Abeta) antibody injected into the third ventricle of mice is distributed throughout the brain within 24 hr and is completely washed out of brain within 36 hr after injection and that, in Tg2576 animals, a single injection of antibody reduces cerebral Abeta and restores presynaptic deficits 1 month after injection without producing hemorrhage or inflammation at an early plaque stage. Here we report the effects of a single ICV injection of anti-Abeta antibody on cerebral levels of immunoreactive Abeta and of microglial activation measured by immunoreactive interleukin-1beta (IL-1beta) at 1, 4, and 8 weeks after injections in TgCRND8 mice at two ages, 2 months (sparse plaques) and 8 months (abundant plaques). The data show that parenchymal amyloid accumulates before cerebral microvascular amyloid and that a single ICV injection reduces only parenchymal amyloid by about 70%, without affecting vascular amyloid, and reduces microglial activation by 46-60% at 1 week after injection. The reappearance of plaques after antibody injection takes 4-8 weeks, whereas plaque-associated focal microglial activation begins increasing between 1 and 4 weeks, suggesting that accumulation of nonfibrillar oligomeric Abeta may account for the earlier onset of microglial activation. No perivascular hemorrhage or inflammation was observed. These results suggest that periodic intraventricular administration of anti-Abeta is a potentially useful method for rapid reduction of both preexisting amyloid load and associated inflammation, providing a window of 4 weeks' duration for possible pharmacological cotreatment(s) to prevent de novo Abeta formation. This ICV method of passive immunization may be safer than active immunization, which has been known to produce encephalitis, or systemic passive immunization, which exposes amyloid-laden cerebral microvasculature to high levels of antibody in the blood and the potential of perivascular hemorrhages.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0360-4012
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
78
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
732-41
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15478192-Age Factors, pubmed-meshheading:15478192-Aging, pubmed-meshheading:15478192-Amyloid beta-Peptides, pubmed-meshheading:15478192-Amyloid beta-Protein Precursor, pubmed-meshheading:15478192-Analysis of Variance, pubmed-meshheading:15478192-Animals, pubmed-meshheading:15478192-Antibodies, Anti-Idiotypic, pubmed-meshheading:15478192-Cell Count, pubmed-meshheading:15478192-Congo Red, pubmed-meshheading:15478192-Female, pubmed-meshheading:15478192-Humans, pubmed-meshheading:15478192-Immunohistochemistry, pubmed-meshheading:15478192-Interleukin-1, pubmed-meshheading:15478192-Male, pubmed-meshheading:15478192-Mice, pubmed-meshheading:15478192-Mice, Inbred C57BL, pubmed-meshheading:15478192-Mice, Transgenic, pubmed-meshheading:15478192-Microglia, pubmed-meshheading:15478192-Plaque, Amyloid, pubmed-meshheading:15478192-Staining and Labeling, pubmed-meshheading:15478192-Third Ventricle, pubmed-meshheading:15478192-Time Factors
pubmed:year
2004
pubmed:articleTitle
Effect of age on the duration and extent of amyloid plaque reduction and microglial activation after injection of anti-Abeta antibody into the third ventricle of TgCRND8 mice.
pubmed:affiliation
Research and Development, Jesse Brown VA Medical Center, Chicago, Illinois 60612, USA. nchauhan@uic.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't