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

Acta Neuropathol. 2012 Jul;124(1):37-50. doi: 10.1007/s00401-012-0964-x. Epub 2012 Feb 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / metabolism*
  • Brain / metabolism*
  • Brain / pathology*
  • Brain Diseases / pathology*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Frontotemporal Lobar Degeneration / pathology
  • Humans
  • Immunohistochemistry
  • Multiple System Atrophy / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Parkinson Disease / pathology
  • alpha-Synuclein / immunology*
  • alpha-Synuclein / metabolism


  • Antibodies
  • alpha-Synuclein