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An antibody with hi...
An antibody with high reactivity for disease-associated α-synuclein reveals extensive brain pathology
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Kovacs, Gabor G. (author)
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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, Irina (author)
- Uppsala universitet,Molekylär och morfologisk patologi
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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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(creator_code:org_t)
- 2012-02-28
- 2012
- English.
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 124:1, s. 37-50
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Keyword
- Pathology
- Patologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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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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show more...
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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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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Clinical Laborat ...
- Articles in the publication
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Acta Neuropathol ...
- By the university
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Uppsala University