Journal
JOURNAL OF CONTROLLED RELEASE
Volume 243, Issue -, Pages 1-10Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2016.09.019
Keywords
VHH; Blood-brain barrier; In vivo imaging; Alzheimer's disease; Tau; Abeta
Funding
- Institut Roche de Recherche et Medecine Translationnelle [1799764611]
- Foundation France Alzheimer [AP2014 758321]
- Foundation Georges Pompidou
- program Investissements d'avenir [ANR-10-IAIHU-06]
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Detection of intracerebral targets with imaging probes is challenging due to the non-permissive nature of blood-brain barrier (BBB). The present work describes two novel single-domain antibodies (VHHs or nanobodies) that specifically recognize extracellular amyloid deposits and intracellular tau neurofibrillary tangles, the two core lesions of Alzheimer's disease (AD). Following intravenous administration in transgenic mouse models of AD, in vivo real-time two-photon microscopy showed gradual extravasation of the VHHs across the BBB, diffusion in the parenchyma and labeling of amyloid deposits and neurofibrillary tangles. Our results demonstrate that VHHs can be used as specific BBB-permeable probes for both extracellular and intracellular brain targets and suggest new avenues for therapeutic and diagnostic applications in neurology. (C) 2016 Elsevier B.V. All rights reserved.
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