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J Mol Neurosci. 2018 Sep;66(1):1-9. doi: 10.1007/s12031-018-1139-6. Epub 2018 Jul 31.

A Novel scFv Anti-Aβ Antibody Reduces Pathological Impairments in APP/PS1 Transgenic Mice via Modulation of Inflammatory Cytokines and Aβ-related Enzymes.

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Department of Physiology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
Department of Physiology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.


Immunotherapy for Alzheimer's disease (AD) remains promising in the improvement of cognition and memory via the clearing of amyloid-β protein (Aβ) in the AD brain, despite some side effects. Our previous studies demonstrated that the 31-35 sequence of the Aβ molecule was the shortest active center and that polyclonal anti-Aβ31-35 antibody reduced neuronal apoptosis and cognitive impairments induced with acute Aβ application. The present study designed a novel single-chain variable fragment (scFv) monoclonal anti-Aβ31-35 antibody (scFv17) that specifically recognized extracellular Aβ and observed protective effects of scFv17 on pathological impairments in APP/PS1 transgenic mice. We also investigated its cellular and molecular mechanisms and found that scFv17 and 6E10 (a positive control) exhibited similar Aβ-clearing ability and that scFv17 produced a stronger effect in clearing Aβ oligomers than 6E10. scFv17, but not 6E10, enhanced anti-inflammatory responses with significant increases in IL-10 and TGF-β. 6E10 decreased BACE1 levels, and scFv17 significantly increased the level of secreted amyloid precursor protein-α (sAPPα), which is an important physiological neurotrophin from APP generated by α-secretase. 6E10 and scFv17, especially the latter, dramatically down-regulated the expression of neprilysin, which is an enzyme expressed in proportion to Aβ concentration. Therefore, the present study demonstrated that the novel monoclonal anti-Aβ31-35 antibody scFv17 effectively reduced pathological impairments in APP/PS1 transgenic mice via modulation of inflammatory cytokines and Aβ-related enzymes, which supports scFv17 as a new alternative in the current immunotherapy of AD.


APP/PS1 transgenic mice; Amyloid-β protein (Aβ); Anti-Aβ single-chain antibody; Neuroinflammation; Secreted amyloid precursor protein-α (sAPPα); scFv17

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