Combined effects of scanning ultrasound and a tau-specific single chain antibody in a tau transgenic mouse model

Nisbet, Rebecca M., Van der Jeugd, Ann, Leinenga, Gerhard, Evans, Harrison T., Janowicz, Phillip W. and Goetz, Juergen (2017) Combined effects of scanning ultrasound and a tau-specific single chain antibody in a tau transgenic mouse model. Brain, 140 5: 1220-1230. doi:10.1093/brain/awx052


Author Nisbet, Rebecca M.
Van der Jeugd, Ann
Leinenga, Gerhard
Evans, Harrison T.
Janowicz, Phillip W.
Goetz, Juergen
Title Combined effects of scanning ultrasound and a tau-specific single chain antibody in a tau transgenic mouse model
Journal name Brain   Check publisher's open access policy
ISSN 0006-8950
1460-2156
Publication date 2017-05-01
Year available 2017
Sub-type Article (original research)
DOI 10.1093/brain/awx052
Open Access Status Not yet assessed
Volume 140
Issue 5
Start page 1220
End page 1230
Total pages 11
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Abstract Alzheimer’s disease is characterized by the deposition of amyloid-β as extracellular plaques and hyperphosphorylated tau as intracellular neurofibrillary tangles. Tau pathology characterizes not only Alzheimer’s disease, but also many other tauopathies, presenting tau as an attractive therapeutic target. Passive tau immunotherapy has been previously explored; however, because only a small fraction of peripherally delivered antibodies crosses the blood–brain barrier, enters the brain and engages with tau that forms intracellular aggregates, more efficient ways of antibody delivery and neuronal uptake are warranted. In the brain, tau exists as multiple isoforms. Here, we investigated the efficacy of a novel 2N tau isoform-specific single chain antibody fragment, RN2N, delivered by passive immunization in the P301L human tau transgenic pR5 mouse model. We demonstrate that, in treated mice, RN2N reduces anxiety-like behaviour and phosphorylation of tau at distinct sites. When administration of RN2N was combined with focused ultrasound in a scanning mode (scanning ultrasound), RN2N delivery into the brain and uptake by neurons were markedly increased, and efficacy was significantly enhanced. Our study provides evidence that scanning ultrasound is a viable tool to enhance the delivery of biologics across the blood–brain barrier and improve therapeutic outcomes and further presents single-chain antibodies as an alternative to full-length antibodies.
Keyword Blood-brain barrier
Alzheimer's disease
Dementia
Neurofibrillary tangles
Tau
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID ACT900116
DP13300101932
APP1037746
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
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