Efficient Near-Infrared In Vivo Imaging of Amyoid-β Deposits in Alzheimer's Disease Mouse Models

The development of early diagnostic and prognostic tools for the visualization of amyloid- (A) deposits is one important focus of current imaging research. In patients with Alzheimer's disease (AD), non-invasive and efficient detection of soluble and aggregated A is important to determine the immediate success of intervention trails. The novel near infrared- fluorescence (NIRF) probe THK-265 efficiently penetrates the blood-brain barrier and has a strong and efficient binding to cerebral A. Ex vivo microscopy of i) THK-265-labeling of plaques in paraffin-embedded tissue and ii) cerebral cryo-sections after intravenous injection of THK-265 confirmed a systematic increase of the NIRF signal corresponding to A plaque number and size during disease progression. Furthermore, we investigated different stages of plaque formation in amyloid- protein precursor transgenic mice in vivo after intravenous application of THK-265 to evaluate different aggregation levels with NIRF signals. The intensity of the NIRF signal correlated well with the plaque burden, indicating its utility for direct monitoring of A aggregation progression. In summary, our results support the use of the NIRF probe THK-265 for the diagnosis and direct visualization of amyloid deposits and open the possibility for efficient, pre-symptomatic monitoring of A deposition in the aging brain.