Transmigration of beta amyloid specific heavy chain antibody fragments across the in vitro blood–brain barrier

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• 作者：K.S. Rutgers^a ; R.J.A. Nabuurs^b ; S.A.A. van den Berg^a ; G.J. Schenk^c ; M. Rotman^a ; ^b ; C.T. Verrips^d ; S.G. van Duinen^e ; ^f ; M.L. Maat-Schieman^f ; M.A. van Buchem^b ; A.G. de Boer^c ; S.M. van der Maarel^a ; ^{maarel@lumc.nl"" rel=""nofollow}
• 关键词：blood– ; brain barrier ; Alzheimer's disease ; amyloid beta ; antibody ; imaging ; cerebral amyloid angiopathy
• 刊名：Neuroscience
• 出版年：2011
• 出版时间：5 September 2011
• 年：2011
• 卷：190
• 期：Complete
• 页码：37-42
• 全文大小：1127 K

文摘

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).