Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. No disease-modifying strategy to prevent or delay AD progression currently exists. Aβ oligomers (AβOs), rather than monomers or fibrils, are considered as the primary neurotoxic species. Therapeutic approaches that direct against AβOs and promote Aβ clearance may have great value for AD treatment. Results: We here reported a multifunctional superparamagnetic iron oxide nanoparticle conjugated with oligomer-specific scFv antibody W20 and class A scavenger receptor activator XD4 (W20/XD4-SPIONs). Besides the diagnostic value, W20/XD4-SPIONs retained the anti-Aβ properties of W20 and XD4 by inhibiting Aβ aggregation, attenuating AβO-induced cytotoxicity and increasing microglial phagocytosis of Aβ. When applied to APP/PS1 mice, W20/XD4-SPIONs significantly rescued cognitive deficits and alleviated neuropathology of AD mice. Conclusion: These results suggest that W20/XD4-SPIONs show therapeutic benefits for AD. In combination with the early diagnostic property, W20/XD4-SPIONs present as a promising agent for early-stage AD diagnosis and intervention.

Background: Alzheimer’s disease (AD) is an incurable and progressive neurodegenerative disorder. Disease-modifying strategies to prevent or delay AD progression are urgently needed. Aβ oligomers (AβOs), rather than monomers or fibrils, are considered as the most neurotoxic species. Therapeutic approaches that direct against these oligomers and promote Aβ clearance may have great value for AD intervention. Results: We here reported the novel multifunctional nanoparticle W20/XD4-SPIONs, which were constructed by conjugating oligomer-specific scFv antibody W20 and class A scavenger receptor activator XD4 onto superparamagnetic iron oxide nanoparticles (SPIONs). Besides the diagnostic value, W20/XD4-SPIONs retained the properties of W20 and XD4 by inhibiting Aβ aggregation, attenuating AβOs-induced cytotoxicity and increasing microglial phagocytosis of Aβ. When applied to AD transgenic mouse model, W20/XD4-SPIONs significantly rescued cognitive deficits and alleviated neuropathology of AD transgenic mice. Conclusion: These results suggest that W20/XD4-SPIONs are a promising therapeutic agent for AD. As a molecular probe, W20/XD4-SPIONs also specifically and sensitively bind to the AβOs in AD brains to provide an MRI signal, demonstrating that W20/XD4-SPIONs are a promising agent for early-stage AD.