Characteristics And Functions Of A ScFv Antibody Against Aβ42

Alzheimer’s disease (AD) is the most common neurodegenerative disease affectingabout10%of the population over65years of age and40%of those over85years of age.Cardinal pathological changes of AD are extracellular amyloid-beta (Aβ) deposits andintracellular neurofibrillary tangles containing hyperphosphorylated tau in the brain.Although the precise etiology of AD is unclear, the amyloid hypothesis has been veryinfluential in pathogenesis and drug development. Generation of the amyloid β-peptide(Aβ) from the amyloid precursor protein (APP) by β-andγ-cleavage followed by seededaggregation of Aβ42is widely believed to be the initiating event in the pathogenesis of AD.The accumulation of these protein aggregates is accompanied by synaptic dysfunction,inflammation and eventually neuronal death. Because Aβ42aggregates are neurotoxic,numerous strategies to prevent Aβ42aggregation and accumulation are currently studied aspotential ways to treat or prevent AD.Active or passive immunotherapeutics have been hot investigational areas for ADtreatment. However, the clinical trial was halted because6%of the patients developedmeningoencephalitis in2003. Thus, vaccines and antibodies that target conformationalepitopes of amyloids which only occur in the pathological amyloid aggregates rather thanin normal human proteins would be promising strategies to circumvent the side effects.In this study, we characterized a scFv isolated from a human scFv library raisedagainst the Aβ42oligomers, and studied its potential to reduce Aβ42-related pathology.Here, we found that the scFv is bounded to Aβ42oligomer with an affinity of～3.1μM.Moreover, the scFv inhibits the aggregation of various amyloid and Aβ42fibril formation.Furthermore, the scFv ameliorates Aβ42-mediated toxicity in the SH-SY5Y cell line. Thismakes it a promising therapeutic antibody for treatment of AD.These results lay the foundation for the design and development of small novelmolecule drugs for treatment of AD, and exhibit broad applicable prospects asimmunosuppressive agents in clinical diagnosis and treatment of AD.