title: Efficient near-infrared in vivo imaging of amyoid-β deposits in Alzheimer's disease mouse models.
abstract: The development of early diagnostic and prognostic tools for the visualization of amyloid-β (Aβ) 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 Aβ 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 Aβ. 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 Aβ plaque number and size during disease progression. Furthermore, we investigated different stages of plaque formation in amyloid-β 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 Aβ 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 Aβ deposition in the aging brain.
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE) Rostock, Rostock, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Schmidt
authors.forename: Jens
authors.initials: J
authors.lastname: Pahnke
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005456:Fluorescent Dyes; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D011744:Pyrimidinones; D013871:Thiones
chemical_list: C557976:5-(6-hydroxy-4-oxo-2-thioxo-1,2,3,4-tetrahydroxy-5-pyrimidinyl)-2,4-pentadienylidene-2-thioxodihydro-4,6(1H,5H)-pyrimidinedione; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005456:Fluorescent Dyes; D011744:Pyrimidinones; D013871:Thiones