Contrast Enhanced Magnetic Resonance Imaging of Amyloid-β Plaques in a Murine Alzheimer's Disease Model.

Abstract

Early detection of amyloid-β (Aβ) aggregates is a critical step to improve the treatment of Alzheimer's disease (AD) because neuronal damage by the Aβ aggregates occurs before clinical symptoms are apparent. We have previously shown that luminescent conjugated oligothiophenes (LCOs), which are highly specific towards protein aggregates of Aβ, can be used to fluorescently label amyloid plaque in living rodents. We hypothesize that the LCO can be used to target gadolinium to the amyloid plaque and hence make the plaque detectable by T1-weighted magnetic resonance imaging (MRI). A novel LCO-gadolinium construct was synthesized to selectively bind to Aβ plaques and give contrast in conventional T1-weighted MR images after intravenous injection in Tg-APPSwe mice. We found that mice with high plaque-burden could be identified using the LCO-Gd constructs by conventional MRI. Our study shows that MR imaging of amyloid plaques is challenging but feasible, and hence contrast-mediated MR imaging could be a valuable tool for early AD detection.