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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.

Author information

1
Department of Physiology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
2
Department of Physiology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. jinshunqi2009@163.com.

Abstract

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.

KEYWORDS:

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

PMID:
30062438
DOI:
10.1007/s12031-018-1139-6
[Indexed for MEDLINE]

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