ABSTRACT
INTRODUCTION: Amyloid-beta oligomers (AßOs) 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 AßOs in vivo, and we tested the behavioral impact of AßOs injected in rabbits, a species with an amino acid sequence that is nearly identical to the human sequence. METHODS: Intracerebroventricular (ICV) injection with stabilized AßOs was performed. Rabbits were probed for AßO accumulation using ACUMNS (an AßO-selective antibody [ACU193] coupled to magnetic nanostructures). Immunohistochemistry was used to verify AßO presence. Cognitive impairment was evaluated using object location and object recognition memory tests and trace eyeblink conditioning. RESULTS: AßOs in the entorhinal cortex of ICV-injected animals were detected by MRI and confirmed by immunohistochemistry. Injections of AßOs also impaired hippocampal-dependent, but not hippocampal-independent, tasks and the area fraction of bound ACUMNs correlated with the behavioral impairment. DISCUSSION: Accumulation of AßOs can be visualized in vivo by MRI of ACUMNS and the cognitive impairment induced by the AßOs can be followed longitudinally with the novel location memory test.
