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  • Kovacs, Gabor G. (author)

An antibody with high reactivity for disease-associated α-synuclein reveals extensive brain pathology

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • 2012-02-28
  • Springer Science and Business Media LLC,2012
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-171339
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-171339URI
  • https://doi.org/10.1007/s00401-012-0964-xDOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • α-Synuclein is the major protein associated with Lewy body dementia, Parkinson's disease and multiple system atrophy. Since α-synuclein is present in the brain in physiological conditions as a presynaptic protein, it is crucial to characterize disease-associated modifications to develop an in vivo biomarker. With the aim to develop antibodies showing high specificity and sensitivity for disease-associated α-synuclein, synthetic peptides containing different amino acid sequences were used for immunization of mice. After generation of α-synuclein aggregates, ELISA and immunoblotting were used to test the specificity of antibodies. Tissue microarray sections originating from different human α-synucleinopathies were used to compare immunostaining with other, commercially available antibodies. Immunization of mice with the peptide TKEGVVHGVATVAE (amino acid 44-57 of α-synuclein) resulted in the generation of a monoclonal antibody (5G4), which was able to bind aggregated α-synuclein preparation in sandwich ELISA or coated on magnetic beads. 5G4 proved to be superior to other antibodies in comparative immunohistochemical studies by revealing more widespread and distinct α-synuclein pathology. Immunoblotting of human brain tissue revealed an additional band seen in dementia with Lewy bodies, whereas the band representing monomeric α-synuclein was very weak or lacking. In summary, the 5G4 antibody is most promising for re-evaluation of archival material and may offer new perspective for the development of in vivo diagnostic assays for detecting disease-associated α-synuclein in body fluids.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Wagner, Uta (author)
  • Dumont, Benoit (author)
  • Pikkarainen, Maria (author)
  • Osman, Awad A. (author)
  • Streichenberger, Nathalie (author)
  • Leisser, Irene (author)
  • Verchère, Jérémy (author)
  • Baron, Thierry (author)
  • Alafuzoff, IrinaUppsala universitet,Molekylär och morfologisk patologi(Swepub:uu)irial548 (author)
  • Budka, Herbert (author)
  • Perret-Liaudet, Armand (author)
  • Lachmann, Ingolf (author)
  • Uppsala universitetMolekylär och morfologisk patologi (creator_code:org_t)

Related titles

  • In:Acta Neuropathologica: Springer Science and Business Media LLC124:1, s. 37-500001-63221432-0533

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