Aβ oligomer induced cognitive impairment and evaluation of ACU193-MNS-based MRI in rabbit

Abstract

Introduction: Amyloid-beta oligomers (AβOs) accumulate in Alzheimer's disease and may instigate neuronal pathology and cognitive impairment. We examined the ability of a new probe for molecular magnetic resonance imaging (MRI) to detect AβOs in vivo, and we tested the behavioral impact of AβOs injected in rabbits, a species with an amino acid sequence that is nearly identical to the human sequence. Methods: Intracerebroventricular (ICV) injection with stabilized AβOs was performed. Rabbits were probed for AβO accumulation using ACUMNS (an AβO-selective antibody [ACU193] coupled to magnetic nanostructures). Immunohistochemistry was used to verify AβO presence. Cognitive impairment was evaluated using object location and object recognition memory tests and trace eyeblink conditioning. Results: AβOs in the entorhinal cortex of ICV-injected animals were detected by MRI and confirmed by immunohistochemistry. Injections of AβOs also impaired hippocampal-dependent, but not hippocampal-independent, tasks and the area fraction of bound ACUMNs correlated with the behavioral impairment. Discussion: Accumulation of AβOs can be visualized in vivo by MRI of ACUMNS and the cognitive impairment induced by the AβOs can be followed longitudinally with the novel location memory test.