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

Abstract

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.

Keywords

• Alzheimer's disease
• amyloid‐beta oligomers
• biomarkers
• dementia
• diagnostics
• eyeblink conditioning