title: Transmigration of beta amyloid specific heavy chain antibody fragments across the in vitro blood-brain barrier.
abstract: Previously selected amyloid beta recognizing heavy chain antibody fragments (VHH) affinity binders derived from the Camelid heavy chain antibody repertoire were tested for their propensity to cross the blood-brain barrier (BBB) using an established in vitro BBB co-culture system. Of all tested VHH, ni3A showed highest transmigration efficiency which is, in part, facilitated by a three amino acid substitutions in its N-terminal domain. Additional studies indicated that the mechanism of transcellular passage of ni3A is by active transport. As VHH ni3A combines the ability to recognize amyloid beta and to cross the BBB, it has potential as a tool for non-invasive in vivo imaging and as efficient local drug targeting moiety in patients suffering from cerebral amyloidosis such as Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA).
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: K S
authors.initials: KS
authors.lastname: Rutgers
authors.forename: R J A
authors.initials: RJ
authors.lastname: Nabuurs
authors.forename: S A A
authors.initials: SA
authors.lastname: van den Berg
authors.forename: G J
authors.initials: GJ
authors.lastname: Schenk
authors.forename: M
authors.initials: M
authors.lastname: Rotman
authors.forename: C T
authors.initials: CT
authors.lastname: Verrips
authors.forename: S G
authors.initials: SG
authors.lastname: van Duinen
authors.forename: M L
authors.initials: ML
authors.lastname: Maat-Schieman
authors.forename: M A
authors.initials: MA
authors.lastname: van Buchem
authors.forename: A G
authors.initials: AG
authors.lastname: de Boer
authors.forename: S M
authors.initials: SM
authors.lastname: van der Maarel
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000276:immunology*; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004314:Down Syndrome / Q000378:metabolism; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D007128:Immunoglobulin Fragments; D007143:Immunoglobulin Heavy Chains