| First Author | Sebollela A | Year | 2017 |
| Journal | J Neurochem | Volume | 142 |
| Issue | 6 | Pages | 934-947 |
| PubMed ID | 28670737 | Mgi Jnum | J:348173 |
| Mgi Id | MGI:6286640 | Doi | 10.1111/jnc.14118 |
| Citation | Sebollela A, et al. (2017) A human scFv antibody that targets and neutralizes high molecular weight pathogenic amyloid-beta oligomers. J Neurochem 142(6):934-947 |
| abstractText | Brain accumulation of soluble oligomers of the amyloid-beta peptide (AbetaOs) is increasingly considered a key early event in the pathogenesis of Alzheimer's disease (AD). A variety of AbetaO species have been identified, both in vitro and in vivo, ranging from dimers to 24mers and higher order oligomers. However, there is no consensus in the literature regarding which AbetaO species are most germane to AD pathogenesis. Antibodies capable of specifically recognizing defined subpopulations of AbetaOs would be a valuable asset in the identification, isolation, and characterization of AD-relevant AbetaO species. Here, we report the characterization of a human single chain antibody fragment (scFv) denoted NUsc1, one of a number of scFvs we have identified that stringently distinguish AbetaOs from both monomeric and fibrillar Abeta. NUsc1 readily detected AbetaOs previously bound to dendrites in cultured hippocampal neurons. In addition, NUsc1 blocked AbetaO binding and reduced AbetaO-induced neuronal oxidative stress and tau hyperphosphorylation in cultured neurons. NUsc1 further distinguished brain extracts from AD-transgenic mice from wild type (WT) mice, and detected endogenous AbetaOs in fixed AD brain tissue and AD brain extracts. Biochemical analyses indicated that NUsc1 targets a subpopulation of AbetaOs with apparent molecular mass greater than 50 kDa. Results indicate that NUsc1 targets a particular AbetaO species relevant to AD pathogenesis, and suggest that NUsc1 may constitute an effective tool for AD diagnostics and therapeutics. |
