X-34, a lipophilic, highly fluorescent derivative of
Congo red, was examined as a histochemical
stain for pathological changes in
Alzheimer's disease (AD).
X-34 intensely stained neuritic and diffuse plaques, neurofibrillary tangles (NFTs), neuropil threads, and cerebrovascular
amyloid. Comparison to standard methods of demonstrating AD pathology showed that
X-34 correlated well with Bielschowsky and
thioflavin-S staining.
X-34 staining of NFTs correlated closely with anti-TAU antibody staining. A 1:1 correspondence of
X-34 and anti-A beta antibody staining of plaques and cerebrovascular
amyloid was observed. Both
X-34 and
thioflavin-S staining were eliminated by
formic acid pretreatment, suggesting that beta-sheet secondary protein structure is a necessary determinant of staining.
X-34 may be a general
amyloid stain, like
Congo red, because it also stains systemic
amyloid deposits due to lambda-light chain
monoclonal gammopathy. In conclusion,
X-34 is a highly fluorescent marker for beta-sheet structures and intensely labels
amyloid plaques, NFTs, neuropil threads, and vascular
amyloid in AD brains. It can be used with both
paraffin-embedded and frozen tissues as well as in combination with immunohistochemistry for double labeling. The intensity of staining and the simplicity and reproducibility of the technique suggest that it may be a useful addition to the standard techniques for evaluation of AD neuropathology. (J Histochem Cytochem 48:1223-1232, 2000)