In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe.
As Alzheimer's disease pathogenesis is associated with the formation of insoluble aggregates of amyloid beta-peptide, approaches allowing the direct, noninvasive visualization of plaque growth in vivo would be beneficial for biomedical research. Here we describe the synthesis and characterization of the near-infrared fluorescence oxazine dye AOI987, which readily penetrates the intact blood-brain barrier and binds to amyloid plaques. Using near-infrared fluorescence imaging, we demonstrated specific interaction of AOI987 with amyloid plaques in APP23 transgenic mice in vivo, as confirmed by postmortem analysis of brain slices. Quantitative analysis revealed increasing fluorescence signal intensity with increasing plaque load of the animals, and significant binding of AOI987 was observed for APP23 transgenic mice aged 9 months and older. Thus, AOI987 is an attractive probe to noninvasively monitor disease progression in animal models of Alzheimer disease and to evaluate effects of potential Alzheimer disease drugs on the plaque load.
Hintersteiner
Martin
M
Discovery Technologies, Novartis Institutes for Biomedical Research, CH-4002 Basel, Switzerland.
Enz
Albert
A
Frey
Peter
P
Jaton
Anne-Lise
AL
Kinzy
Willy
W
Kneuer
Rainer
R
Neumann
Ulf
U
Rudin
Markus
M
Staufenbiel
Matthias
M
Stoeckli
Markus
M
Wiederhold
Karl-Heinz
KH
Gremlich
Hans-Ulrich
HU
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005456:Fluorescent Dyes; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods*; D010078:Oxazines; D013055:Spectrophotometry, Infrared / Q000379:methods*; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D010078:Oxazines