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

Nicholas B. Rozema, Daniele Procissi, Nicola Bertolino, Kirsten L. Viola, Vikas Nandwana, Nafay Abdul, Sophia Pribus, Vinayak Dravid, William L. Klein, John F. Disterhoft, Craig Weiss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere12087
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Volume6
Issue number1
DOIs
StatePublished - 2020

Keywords

  • Alzheimer's disease
  • amyloid-beta oligomers
  • biomarkers
  • dementia
  • diagnostics
  • eyeblink conditioning
  • magnetic resonance imaging

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health

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