Evaluation of α-synuclein immunohistochemical methods used by invited experts

Thomas G. Beach, Charles L. White, Ronald L. Hamilton, John E. Duda, Takeshi Iwatsubo, Dennis W. Dickson, James B. Leverenz, Federico Roncaroli, Manuel Buttini, Christa L. Hladik, Lucia I. Sue, Joseph V. Noorigian, Charles H. Adler

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

The use of α-synuclein immunohistochemistry has altered our concepts of the cellular pathology, anatomical distribution and prevalence of Lewy body disorders. However, the diversity of methodology between laboratories has led to some inconsistencies in the literature. Adoption of uniformly sensitive methods may resolve some of these differences. Eight different immunohistochemical methods for demonstrating α-synuclein pathology, developed in eight separate expert laboratories, were evaluated for their sensitivity for neuronal elements affected by human Lewy body disorders. Identical test sets of formalin-fixed, paraffin-embedded sections from subjects diagnosed neuropathologically with or without Lewy body disorders were stained with the eight methods and graded by three observers for specific and nonspecific staining. The methods did not differ significantly in terms of Lewy body counts, but varied considerably in their ability to reveal neuropil elements such as fibers and dots. One method was clearly superior for revealing these neuropil elements and the critical factor contributing to its high sensitivity was considered to be its use of proteinase K as an epitope retrieval method. Some methods, however, achieved relatively high sensitivities with optimized formic acid protocols combined with a hydrolytic step. One method was developed that allows high sensitivity with commercially available reagents.

Original languageEnglish (US)
Pages (from-to)277-288
Number of pages12
JournalActa neuropathologica
Volume116
Issue number3
DOIs
StatePublished - Jul 15 2008

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Beach, T. G., White, C. L., Hamilton, R. L., Duda, J. E., Iwatsubo, T., Dickson, D. W., Leverenz, J. B., Roncaroli, F., Buttini, M., Hladik, C. L., Sue, L. I., Noorigian, J. V., & Adler, C. H. (2008). Evaluation of α-synuclein immunohistochemical methods used by invited experts. Acta neuropathologica, 116(3), 277-288. https://doi.org/10.1007/s00401-008-0409-8