The search for a peripheral biopsy indicator of a-synuclein pathology for Parkinson disease

John M. Lee, Pascal Derkinderen, Jeffrey H. Kordower, Roy Freeman, David G. Munoz, Thomas Kremer, Wagner Zago, Samantha J. Hutten, Charles H. Adler, Geidy E. Serrano, Thomas G. Beach

Research output: Contribution to journalReview article

43 Scopus citations

Abstract

The neuropathological hallmark of Parkinson disease (PD) is abnormal accumulation of a-synuclein (a-syn). Demonstrating pathological a-syn in live patients would be useful for identifying and monitoring PD patients. To date, however, imaging and biofluid approaches have not permitted premortem assessment of pathological a-syn. a-syn pathology in the peripheral nervous system of patients with PD has been demonstrated in studies dating back more than 40 years. More recent work suggests that colon, submandibular gland and skin biopsies could be useful as expedient biomarkers but histological differentiation of pathological and normal peripheral a-syn has been challenging and multiple research groups have reported variable results. A variety of immunohistochemical methods have been employed but almost all studies to date originated at single centers with no independent, blinded replication. To address these issues, the Michael J. Fox Foundation for Parkinson's Research sponsored a series of meetings and investigations by several research groups with relevant experience. The major finding reported herein was that biopsies can be used to distinguish PD patients from normal subjects. However, full assessment of the clinical potential of biopsy will only be achieved through large, multicenter trials in which both the initial detection methodology and histology have been assessed by blinded panels of pathologists.

Original languageEnglish (US)
Pages (from-to)2-15
Number of pages14
JournalJournal of Neuropathology and Experimental Neurology
Volume76
Issue number1
DOIs
StatePublished - 2017

Keywords

  • Biomarker
  • Colon
  • Diagnosis
  • Lewy body
  • Prognosis
  • Skin
  • Submandibular gland

ASJC Scopus subject areas

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

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  • Cite this

    Lee, J. M., Derkinderen, P., Kordower, J. H., Freeman, R., Munoz, D. G., Kremer, T., Zago, W., Hutten, S. J., Adler, C. H., Serrano, G. E., & Beach, T. G. (2017). The search for a peripheral biopsy indicator of a-synuclein pathology for Parkinson disease. Journal of Neuropathology and Experimental Neurology, 76(1), 2-15. https://doi.org/10.1093/jnen/nlw103