uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Establishing the fluorescent amyloid ligand h-FTAA for studying human tissues with systemic and localized amyloid
Linkoping Univ, IFM Dept Chem, SE-58183 Linkoping, Sweden..
Univ Kiel, Inst Pathol, Kiel, Germany..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Show others and affiliations
2016 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 23, no 2, 98-108 p.Article in journal (Refereed) PublishedText
Abstract [en]

Rapid and accurate detection of amyloid deposits in routine surgical pathology settings are of great importance. The use of fluorescence microscopy in combination with appropriate amyloid specific dyes is very promising in this regard. Here we report that a luminescent conjugated oligothiophene, h-FTAA, rapidly and with high sensitivity and selectivity detects amyloid deposits in verified clinical samples from systemic amyloidosis patients with AA, AL and ATTR types; as well as in tissues laden with localized amyloidosis of AANF, AIAPP and ASem1 type. The probe h-FTAA emitted yellow red fluorescence on binding to amyloid deposits, whereas no apparent staining was observed in surrounding tissue. The only functional structure stained with h-FTAA showing the amyloidotypic fluorescence spectrum was Paneth cell granules in intestine. Screening of 114 amyloid containing tissues derived from 107 verified (Congo red birefringence and/or immunohistochemistry) amyloidosis patients revealed complete correlation between h-FTAA and Congo red fluorescence (107/107, 100% sensitivity). The majority of Congo red negative control cases (27 of 32, 85% specificity) were negative with h-FTAA. Small Congo red negative aggregates in kidney, liver, pancreas and duodenum were found by h-FTAA fluorescence in five control patients aged 72-83 years suffering from diverse diseases. The clinical significance of these false-positive lesions is currently not known. Because h-FTAA fluorescence is one magnitude brighter than Congo red and as the staining is performed four magnitudes lower than the concentration of dye, we believe that these inclusions are beyond detection by Congo red. We conclude that h-FTAA is a fluorescent hypersensitive, rapid and powerful tool for identifying amyloid deposits in tissue sections. Use of h-FTAA can be exploited as a rapid complementary technique for accurate detection of amyloid in routine surgical pathology settings. Our results also implicate the potential of the technique for detection of prodromal amyloidosis as well as for discovery of new amyloid-like protein aggregates in humans.

Place, publisher, year, edition, pages
2016. Vol. 23, no 2, 98-108 p.
Keyword [en]
Amyloidosis, Congo red, diagnosis, fluorescence, microscopy, oligothiophenes, screening
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-297765DOI: 10.3109/13506129.2016.1158159ISI: 000375905000004PubMedID: 26987044OAI: oai:DiVA.org:uu-297765DiVA: diva2:943685
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)Swedish Research CouncilGöran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of TechnologyEU, European Research CouncilEU, FP7, Seventh Framework Programme
Available from: 2016-06-28 Created: 2016-06-28 Last updated: 2016-06-28Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Westermark, PerWestermark, Gunilla T.
By organisation
Department of Immunology, Genetics and PathologyDepartment of Medical Cell Biology
In the same journal
Amyloid: Journal of Protein Folding Disorders
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 199 hits
ReferencesLink to record
Permanent link

Direct link