Abstract
BackgroundAlzheimer’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.ResultsWe here reported a multifunctional superparamagnetic iron oxide nanoparticle conjugated with Aβ 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.ConclusionThese 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.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder
We previously demonstrated that W20/XD4-superparamagnetic iron oxide nanoparticles (SPIONs), as an Aβ oligomers (AβOs)-targeted molecular MRI contrast probe, exhibited early diagnostic potentials for AD [16]
The characterization of W20/XD4‐SPIONs W20/XD4-SPIONs were constructed by conjugating W20 antibody and XD4 peptide onto the PEG-coated SPIONs (Fig. 1a)
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. Aβ oligomers (AβOs), rather than monomers or fibrils, are considered as the primary neurotoxic species. Alzheimer’s disease (AD) is the most common neurodegenerative disorder, which is characterized by progressive memory loss and cognitive decline. The amyloid cascade hypothesis suggests that Aβ oligomers (AβOs), rather than monomers or insoluble fibrils, are the primary toxic species in the pathogenesis of AD [3]. AβOs appear in the brains of AD patients decades before the onset of clinical symptoms [4,5,6], Liu et al J Nanobiotechnol (2020) 18:160 suggesting their potential use as a more appealing target than plaques at the early stage of AD. The Biologics License Application of aducanumab, a specific anti-AβOs antibody, has been submitted to FDA after the significant therapeutic efficacy in phase III clinical trials was obtained [11]
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