Anti-A beta single-chain variable fragment antibodies restore memory acquisition in a Drosophila model of Alzheimer's disease

作者：Martin Pena Alfonso^*; Rincon Limas Diego E; Fernandez Funez Pedro^*

来源：Scientific Reports, 2017, 7(1): 11268.

DOI：10.1038/s41598-017-11594-2

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder triggered by the accumulation of soluble assemblies of the amyloid-beta 42 (A beta 42) peptide. Despite remarkable advances in understanding the pathogenesis of AD, the development of palliative therapies is still lacking. Engineered anti-A beta 42 antibodies are a promising strategy to stall the progression of the disease. Single-chain variable fragment (scFv) antibodies increase brain penetration and offer flexible options for delivery while maintaining the epitope targeting of full antibodies. Here, we examined the ability of two anti-A beta scFv antibodies targeting the N-terminal (scFv9) and C-terminal (scFv42.2) regions of A beta 42 to suppress the progressive memory decline induced by extracellular deposition of A beta 42 in Drosophila. Using olfactory classical conditioning, we observe that both scFv antibodies significantly improve memory performance in flies expressing A beta 42 in the mushroom body neurons, which are intimately involved in the coding and storage of olfactory memories. The scFvs effectively restore memory at all ages, from one-day post-eclosion to thirty-day-old flies, proving their ability to prevent the toxicity of different pathogenic assemblies. These data support the application of this paradigm of A beta 42-induced memory loss in Drosophila to investigate the protective activity of A beta 42-binding agents in an AD-relevant functional assay.

• 出版日期2017-9-12