X-34, A Fluorescent Derivative of Congo Red: A Novel Histochemical Stain for Alzheimer's Disease Pathology

Styren, Scot; Hamilton, Ronald L.; Styren, Gisele C.; Klunk, William E.

doi:10.1177/002215540004800906

Cited by 258 publications

(211 citation statements)

References 20 publications

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“…Interestingly, the species of A␤ that coimmunoprecipitated with HSP-16 appeared to be predominantly multimeric. To determine whether this A␤͞HSP-16 interaction occurs in vivo, CL2006 transgenic animals were fixed and probed with mAb 4G8, the amyloid-specific dye X-34 (29), and anti-HSP-16 antibody. HSP-16 was found to tightly colocalize with immunoreactive A␤ deposits but not with the fully amyloidic A␤ detected by X-34.…”

Section: Resultsmentioning

confidence: 99%

Interaction of intracellular β amyloid peptide with chaperone proteins

Fonte

Kapulkin²,

Taft³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

197

151

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Expression of the human β amyloid peptide (Aβ) in transgenic Caenorhabditis elegans animals can lead to the formation of intracellular immunoreactive deposits as well as the formation of intracellular amyloid. We have used this model to identify proteins that interact with intracellular Aβ in vivo . Mass spectrometry analysis of proteins that specifically coimmunoprecipitate with Aβ has identified six likely chaperone proteins: two members of the HSP70 family, three αB-crystallin-related small heat shock proteins (HSP-16s), and a putative ortholog of a mammalian small glutamine-rich tetratricopeptide repeat-containing protein proposed to regulate HSP70 function. Quantitative reverse transcription–PCR analysis shows that the small heat shock proteins are also transcriptionally induced by Aβ expression. Immunohistochemistry demonstrates that HSP-16 protein closely colocalizes with intracellular Aβ in this model. Transgenic animals expressing a nonaggregating Aβ variant, a single-chain Aβ dimer, show an altered pattern of coimmunoprecipitating proteins and an altered cellular distribution of HSP-16. Double-stranded RNA inhibition of R05F9.10, the putative C. elegans ortholog of the human small glutamine-rich tetratricopeptide-repeat-containing protein (SGT), results in suppression of toxicity associated with Aβ expression. These results suggest that chaperone function can play a role in modulating intracellular Aβ metabolism and toxicity.

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Section: Resultsmentioning

confidence: 99%

Interaction of intracellular β amyloid peptide with chaperone proteins

Fonte

Kapulkin²,

Taft³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

197

151

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“…6A, d and e) and fluorescent staining with thioflavin S and X-34 (Fig. 6A, a and c) (36). Positive neurons were abundant in brain and spinal cord of all tau-P301L mice of 9 months and older and absent or weak in CNS of younger tau-P301L mice.…”

Section: Tauopathy and Conformational Epitopes Characterize Tau-p301lmentioning

confidence: 82%

“…Finally, the sections were mounted in 10% Mowiol, 25% glycerol, 100 mM Tris⅐HCl (pH 8.5), 40 mg/ml triethylenediamine. Staining with X-34, a derivative of Congo Red that stains ␤-pleated proteins, was carried out essentially as described (36). Sections were washed twice for 2 min in PBS and incubated in 0.1 mM X-34 in 40% ethanol.…”

Section: Methodsmentioning

confidence: 99%

Changed Conformation of Mutant Tau-P301L Underlies the Moribund Tauopathy, Absent in Progressive, Nonlethal Axonopathy of Tau-4R/2N Transgenic Mice

Terwel

Lasrado

Snauwaert

et al. 2005

Journal of Biological Chemistry

235

366

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Protein tau-3R/4R isoform ratio and phosphorylation regulates binding to microtubules and, when disturbed by aging or mutations, results in diverse tauopathies and in neurodegeneration. The underlying mechanisms were studied here in three transgenic mouse strains with identical genetic background, all expressing the tau-4R/2N isoform driven specifically in neurons by the thy1 gene promoter. Two strains, expressing human tau-4R/2N or mutant tau-4R/2N-P301L at similar, moderate levels, developed very different phenotypes. Tau-4R/2N mice became motor-impaired already around age 6-8 weeks, accompanied by axonopathy (dilatations, spheroids), but no tau aggregates, and surviving normally. In contrast, tau-P301L mice developed neurofibrillary tangles from age 6 months, without axonal dilatations and, despite only minor motor problems, all succumbing before the age of 13 months. The third strain, obtained by tau knock-out/knock-in (tau-KOKI), expressed normal levels of wild-type human tau-4R/2N replacing all mouse tau isoforms. Tau-KOKI mice survived normally with minor motor problems late in life and without any obvious pathology. Biochemically, a fraction of neuronal tau in aging tau-P301L mice was hyperphosphorylated concomitant with conformational changes and aggregation, but overall, tau-4R/2N was actually more phosphorylated than tau-P301L. Significantly, tau with changed conformation and with hyperphosphorylation colocalized in the same neurons in aging tau-P301L mice. Taken together, we conclude that excessive binding of tau-4R/2N as opposed to reduced binding of tau-P301L to microtubules is responsible for the development of axonopathy and tauopathy, respectively, in tau-4R/2N and tau-P301L mice and that the conformational change of tau-P301L is a major determinant in triggering the tauopathy.

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“…The relaxation times and relaxation rates of CR-BSA-(Gd-DTPA)n and Gd-DTPA in different solutions tissue (Steensma, 2001). Klunk and colleagues have been working for several years to develop amyloid-binding Congo red analogues as in vivo neuroimaging agents (Klunk et al, 1995;Styren et al, 2000). Makoto Higuchi reported a congo red derivative which had been used in 19 F and 1 H magnetic resonance imaging (MRI) for detection of amyloid b plaques (Higuchi et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Detection of Aβ Plaques by a Novel Specific MRI Probe Precursor CR‐BSA‐(Gd‐DTPA)n in APP/PS1 Transgenic Mice

Cui

et al. 2010

The Anatomical Record

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Amyloid plaques are one of the hallmarks of Alzheimer's disease (AD). The lack of specific probes that can detect individual senile plaques in AD has prompted the development of magnetic resonance imaging (MRI) probes. In this study, based on DTPA-gadolinium (III) and congo red (CR), a novel specific MRI probe precursor CR-BSA-(Gd-DTPA)n was successfully synthesized. Its ability to bind to amyloid plaques was evaluated by brain sections from APP/PS1 transgenic mice. Its specificity for Ab plaques was further demonstrated by immunohistochemistry (IHC) staining with the monoclonal antibody to the Ab protein. Meanwhile, the amyloid deposits detected by the CR-BSA-(Gd-DTPA)n were matched to the amyloid deposits detected by Ab specific antibody. We also found that a few amyloid-like deposits which was not detected by IHC. The findings indicated that the probe perhaps could detect the neurofibrillary tangles (NFT) similar to the effect of CR itself, and this will be verified in future experiments. The works suggested that the Ab protein-specific magnetic resonance contrast agent precursor CR-BSA-(Gd-DTPA)n can be used as a potential fluorescence and MR multi-modal imaging probe precursor to display individual senile plaques in AD. Anat Rec, 293:2136Rec, 293: -2143

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X-34, A Fluorescent Derivative of Congo Red: A Novel Histochemical Stain for Alzheimer's Disease Pathology

Cited by 258 publications

References 20 publications

Interaction of intracellular β amyloid peptide with chaperone proteins

Interaction of intracellular β amyloid peptide with chaperone proteins

Changed Conformation of Mutant Tau-P301L Underlies the Moribund Tauopathy, Absent in Progressive, Nonlethal Axonopathy of Tau-4R/2N Transgenic Mice

Detection of Aβ Plaques by a Novel Specific MRI Probe Precursor CR‐BSA‐(Gd‐DTPA)n in APP/PS1 Transgenic Mice

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