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PLoS One. 2010 May 11;5(5):e10549. doi: 10.1371/journal.pone.0010549.

Antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-beta plaque load in the TgCRND8 mouse model of Alzheimer's disease.

Author information

1
Brain Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.

Abstract

Immunotherapy for Alzheimer's disease (AD) relies on antibodies directed against toxic amyloid-beta peptide (Abeta), which circulate in the bloodstream and remove Abeta from the brain. In mouse models of AD, the administration of anti-Abeta antibodies directly into the brain, in comparison to the bloodstream, was shown to be more efficient at reducing Abeta plaque pathology. Therefore, delivering anti-Abeta antibodies to the brain of AD patients may also improve treatment efficiency. Transcranial focused ultrasound (FUS) is known to transiently-enhance the permeability of the blood-brain barrier (BBB), allowing intravenously administered therapeutics to enter the brain. Our goal was to establish that anti-Abeta antibodies delivered to the brain using magnetic resonance imaging-guided FUS (MRIgFUS) can reduce plaque pathology. To test this, TgCRND8 mice received intravenous injections of MRI and FUS contrast agents, as well as anti-Abeta antibody, BAM-10. MRIgFUS was then applied transcranially. Within minutes, the MRI contrast agent entered the brain, and BAM-10 was later found bound to Abeta plaques in targeted cortical areas. Four days post-treatment, Abeta pathology was significantly reduced in TgCRND8 mice. In conclusion, this is the first report to demonstrate that MRIgFUS delivery of anti-Abeta antibodies provides the combined advantages of using a low dose of antibody and rapidly reducing plaque pathology.

PMID:
20485502
PMCID:
PMC2868024
DOI:
10.1371/journal.pone.0010549
[Indexed for MEDLINE]
Free PMC Article

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