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An antibody with hi...
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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 ...
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2012-02-28
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Springer Science and Business Media LLC,2012
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-171339
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-171339URI
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https://doi.org/10.1007/s00401-012-0964-xDOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
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Wagner, Uta
(author)
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Dumont, Benoit
(author)
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Pikkarainen, Maria
(author)
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Osman, Awad A.
(author)
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Streichenberger, Nathalie
(author)
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Leisser, Irene
(author)
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Verchère, Jérémy
(author)
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Baron, Thierry
(author)
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Alafuzoff, IrinaUppsala universitet,Molekylär och morfologisk patologi(Swepub:uu)irial548
(author)
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Budka, Herbert
(author)
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Perret-Liaudet, Armand
(author)
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Lachmann, Ingolf
(author)
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Uppsala universitetMolekylär och morfologisk patologi
(creator_code:org_t)
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In:Acta Neuropathologica: Springer Science and Business Media LLC124:1, s. 37-500001-63221432-0533
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Kovacs, Gabor G.
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Wagner, Uta
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Dumont, Benoit
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Pikkarainen, Mar ...
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Osman, Awad A.
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Streichenberger, ...
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Leisser, Irene
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Verchère, Jérémy
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Baron, Thierry
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Alafuzoff, Irina
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Budka, Herbert
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Perret-Liaudet, ...
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Lachmann, Ingolf
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Uppsala University