Spectral Unmixing Imaging of Wavelength-Responsive Fluorescent Probes: An Application for the Real-Time Report of Amyloid Beta Species in Alzheimer’s Disease
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
The goal of the study was to investigate a method for the real-time assessment of a target concentration in vivo using a combination of a spectral unmixing technique and a fluorescent probe specific for amyloid beta (Aβ) species, the biomarkers for Alzheimer’s disease (AD).
The probe CRANAD-3 has a significant emission wavelength shift upon binding to Aβ species. It was used to differentiate a bound probe from an unbound probe in a phantom, ex vivo in brain slices and whole brain, and in vivo in a transgenic mouse model of AD.
The ex vivo unmixing imaging of AD brain clearly showed differential distribution of the bound and unbound probes between the brain tissue and blood vessels. The in vivo unmixed signals of bound CRANAD-3 reached a plateau with increasing dosage, demonstrating that these signals correspond to Aβ content, not probe injected dose.
This study provided evidence that signals processed by the spectral unmixing technique could be used as a real-time reporter of Aβ species loading in vivo and ex vivo.
- Xu H, Rice BW (2009) In-vivo fluorescence imaging with a multivariate curve resolution spectral unmixing technique. J Biomed Opt 14:064011 CrossRef
- Mayes P, Dicker D, Liu Y, El-Deiry W (2008) Noninvasive vascular imaging in fluorescent tumors using multispectral unmixing. Biotechniques 45:459–464 CrossRef
- Naik S, Piwnica-Worms D (2007) Real-time imaging of beta-catenin dynamics in cells and living mice. Proc Natl Acad Sci USA 104:17465–17470 CrossRef
- Zimmermann T (2005) Spectral imaging and linear unmixing in light microscopy. Adv Biochem Eng Biotechnol 95:245–265
- Liu J, Lau SK, Varma VA, Kairdolf BA, Nie S (2010) Multiplexed detection and characterization of rare tumor cells in Hodgkin's lymphoma with multicolor quantum dots. Anal Chem 82:6237–6243 CrossRef
- Raymond SB, Skoch J, Hills ID, Nesterov EE, Swager TM, Bacskai BJ (2008) Smart optical probes for near-infrared fluorescence imaging of Alzheimer's disease pathology. Eur J Nucl Med Mol Imaging 35:s93–s98 CrossRef
- Ran C, Xu X, Raymond SB et al (2009) Design, synthesis, and testing of difluoroboron-derivatized curcumins as near-infrared probes for in vivo detection of amyloid-beta deposits. J Am Chem Soc 131:15257–15261 CrossRef
- Nesterov EE, Skoch J, Hyman BT, Klunk WE, Bacskai BJ, Swager TM (2005) In vivo optical imaging of amyloid aggregates in brain: design of fluorescent markers. Angew Chem Int Ed Engl 44:5452–5456 CrossRef
- Mizusawa K, Ishida Y, Takaoka Y, Miyagawa M, Tsukiji S, Hamachi I (2010) Disassembly-driven turn-on fluorescent nanoprobes for selective protein detection. J Am Chem Soc 132:7291–7293 CrossRef
- Dickinson ME, Bearman G, Tille S, Lansford R, Fraser SE (2001) Multi-spectral imaging and linear unmixing add a whole new dimension to laser scanning fluorescence microscopy. Biotechniques 31:1272, 1274–1276, 1278
- Ran C, Zhao W, Moir R, Moore A (2011) Non-conjugated small molecule FRET for differentiating monomers from higher molecular weight amyloid beta species. PLoS One 6:e19362 CrossRef
- Selkoe D (2008) Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Behav Brain Res 192:106–113 CrossRef
- Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 8:101–112 CrossRef
- Greenspan P, Fowler SD (1985) Spectrofluorometric studies of the lipid probe, Nile red. J Lipid Res 26:781–789
- Jankowsky JL, Fadale DJ, Anderson J et al (2004) Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13:159–170 CrossRef
- Reiserer RS, Harrison FE, Syverud DC, McDonald MP (2007) Impaired spatial learning in the APPSwe + PSEN1DeltaE9 bigenic mouse model of Alzheimer's disease. Genes Brain Behav 6:54–65 CrossRef
- Hintersteiner M, Enz A, Frey P et al (2005) In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe. Nat Biotechnol 23:577–583 CrossRef
- Gurskaya NG, Verkhusha VV, Shcheglov AS et al (2006) Engineering of a monomeric green-to-red photoactivatable fluorescent protein induced by blue light. Nat Biotechnol 24:461–465 CrossRef
- Lukyanov KA, Chudakov DM, Lukyanov S, Verkhusha VV (2005) Innovation: photoactivatable fluorescent proteins. Nat Rev Mol Cell Biol 6:885–891 CrossRef
- Johnson I (1998) Fluorescent probes for living cell. Histochem J 30:123–140 CrossRef
- Spectral Unmixing Imaging of Wavelength-Responsive Fluorescent Probes: An Application for the Real-Time Report of Amyloid Beta Species in Alzheimer’s Disease
Molecular Imaging and Biology
Volume 14, Issue 3 , pp 293-300
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Spectral unmixing
- Alzheimer’s disease
- Wavelength-responsive fluorescent probe
- Industry Sectors