Visualization of fibrillar amyloid deposits in living, transgenic Caenorhabditis elegans animals using the sensitive amyloid dye, X-34

Transgenic Caenorhabditis elegans animals can be engineered to express high levels of the human beta amyloid peptide (Abeta). Histochemistry of fixed tissue from these animals reveals deposits reactive with the amyloid-specif ic dyes Congo Red and thioflavin S (Fay et al., J. Neurochem 71:1616, 1998) . Here we show by immune-electron microscopy that these animals contain int racellular immunoreactive deposits with classic amyloid fibrillar ultrastru cture. These deposits can be visualized in living animals using the newly d eveloped, intensively fluorescent, amyloid-specific dye X-34. This in vivo staining allows monitoring of amyloid deposition in individual animals over time. The specificity of this staining is demonstrated by examining transg enic animals expressing high levels of a non-fibrillar beta peptide variant , the beta single-chain dimer, These animals have deposits immunoreactive w ith anti-beta antibodies, but do not have X-34 deposits or deposits with a fibrillar ultrastructure. X-34 can also be used in vivo to visualize putati ve amyloid deposits resulting from accumulation of human transthyretin, ano ther amyloidic protein. In vivo amyloid staining with X-34 may be a useful tool for monitoring anti-amyloidic treatments in real time or screening for genetic alterations that affect amyloid formation. (C) 2001 Elsevier Scien ce Inc. All rights reserved.