What kinds of small molecules can be used for fluorescent or luminiscent labelling of Amyloid beta and/or Tau for In-vivo or ex-vivo imaging of the whole brain? We're looking for something that can be injected systemically (Intraperitoneally or intravenously) or at least intracerebroventricularly, that will label these AD hallmarks and which we can detect in vivo.
We welcome other ideas on such molecules that may even be used with incubation of thick sections/blocks of brain (fresh or fixed) extracted from the mouse.
Any help and suggestion is appreciated
Chrysamine G and Pittsburgh B, uncharged analogues of Congo Red and ThT to increase BBB permeability, are commonly used for in vivo imaging.
Small molecules that bind to Abeta in the brain (in vivo) are labeled for positron emission tomography (PET), e.g. Pittsburgh compound B, and similar compounds are in the pipeline to enhance sensitivity, i.e. for rodent brains. It's difficult to detect fluorescent or luminescent signals from deep in the tissue, this requires near IR wavelengths. CCD cameras sensitive in that range exist.
Type this into your browser:
http://www.ncbi.nlm.nih.gov/books/?term=amyloid+AND+Optical+AND+micad[book]+AND+table[type]
to bring up the NIH database of optical contrast reagents for amyloid. More exist besides these.
All the points above are valid but pretty much only for Amyloid, it is difficult to image Tau or NFT in vivo because as far as I am aware there is no specific ligand for Tau that does not bind to amyloid. FDDNP is reported to bind both and so PET imaging with FDDNP is supposed to report both amyloid and Tau. If you have model of Tau pathology (without amyloid) you should be able to image it.
Chrysamine and congo red are fluorescent so if you don't have access to PET, ex vivo fluoresence or in vivo confocal through a cranial windows should give you a partial answer.
Good luck!
Check out this new publication... Journal of Alzheimer’s Disease 31 (2012) 601–612. It describes the development of new PET imaging compounds for Tau pathology. It is proprietary (Siemens) so the compounds are not likely to be shared but it is an interesting paper and points the way for new compounds that may be shared...??
We have developed small molecules that can be used for fluorescent labeling of Amyloid beta and/or potentially Tau (R&D ongoing) for in vivo, ex vivo or in vitro imaging of the brain. It can be injected systemically and will label protein aggregation hallmarks of AD. Our tracer can detected in vivo by for example two-photon microscopy or ex vivo using conventional fluorescence microscopy. Data obtained using our Abeta tracers was presented at SfN in New Oreleans and at ADPD 2013 recently (http://adpd.ekonnect.co/ADPD_443/poster_52081/program.aspx).
You can take a look at this review which resumes the difficulties to have good biomarkers and appropriate techniques for imaging AD hallmarks:
http://www.ncbi.nlm.nih.gov/pubmed/20953404
An extensive list of amyloid fluorophores has been added by Steingrimur Stefansson to a project on this site devoted to amyloid methodology. Message me if you want to get involved.
Regarding Herve Boutin's point, there is apparently one ligand that recognizes tau tangles over amyloid plaques by sensing hyperphosporylation. I do not know if it will work for in vivo imaging.
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