title: The Search for a Peripheral Biopsy Indicator of α-Synuclein Pathology for Parkinson Disease.
abstract: The neuropathological hallmark of Parkinson disease (PD) is abnormal accumulation of α-synuclein (α-syn). Demonstrating pathological α-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 α-syn. α-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 α-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.
authors.affiliation: Department of Pathology, NorthShore University Health System, University of Chicago, Pritzker School of Medicine, Evanston, Illinois, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Inserm, U913, Nantes F-44035; Nantes University, Nantes F-44035; Department of Neurology, CHU Nantes, Nantes F-44093, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Derkinderen
authors.affiliation: Center for Brain Repair, Department of Pathology, Rush Medical College, Chicago, Illinois, USA.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Kordower
authors.affiliation: Harvard Medical School; Center for Autonomic and Peripheral Nerve Disorders, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Freeman
authors.affiliation: Laboratory Medicine and Keenan Research Centre for Biomedical Research of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David G
authors.initials: DG
authors.lastname: Munoz
authors.affiliation: Roche Pharmaceutical Research and Early Development, Nord DTA, Biomarker and Clinical Imaging, Roche Innovation Center, F Hoffman-La Roche, Ltd., Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kremer
authors.affiliation: Prothena Biosciences, Inc., South San Francisco, California
authors.forename: Wagner
authors.initials: W
authors.lastname: Zago
authors.affiliation: Prothena Biosciences, Inc., South San Francisco, California (WZ); Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Hutten
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Adler
authors.affiliation: Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, USA.
authors.forename: Geidy E
authors.initials: GE
authors.lastname: Serrano
authors.affiliation: Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003226:Congresses as Topic / Q000639:trends; D006801:Humans; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013363:Submandibular Gland / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D051844:alpha-Synuclein
keywords: Biomarker; Colon; Diagnosis; Lewy body; Prognosis; Skin; Submandibular gland