Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders

Authors

  • Ellen Gelpi MD,

    1. Neurological Tissue Bank of the Biobanc-Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
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    • Dr. Gelpi and Dr. Navarro-Otano contributed equally to this work.

  • Judith Navarro-Otano MD,

    1. Neurological Tissue Bank of the Biobanc-Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
    2. Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clinic de Barcelona, Barcelona, Spain
    3. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain
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    • Dr. Gelpi and Dr. Navarro-Otano contributed equally to this work.

  • Eduardo Tolosa MD, PhD,

    Corresponding author
    1. Neurological Tissue Bank of the Biobanc-Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
    2. Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clinic de Barcelona, Barcelona, Spain
    3. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain
    • Correspondence to: Dr. Eduardo Tolosa, Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències, Hospital Clínic de Barcelona. c/Villarroel 170, 08036 Barcelona, Spain; etolosa@clinic.ub.es

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  • Carles Gaig MD,

    1. Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clinic de Barcelona, Barcelona, Spain
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  • Yaroslau Compta MD,

    1. Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clinic de Barcelona, Barcelona, Spain
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  • María Jesús Rey MD,

    1. Neurological Tissue Bank of the Biobanc-Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
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  • Maria José Martí MD,

    1. Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clinic de Barcelona, Barcelona, Spain
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  • Isabel Hernández MD,

    1. Fundacio ACE, Barcelona Alzheimer's Treatment and Research Center, Barcelona, Spain
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  • Francesc Valldeoriola MD,

    1. Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clinic de Barcelona, Barcelona, Spain
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  • Ramon Reñé MD,

    1. Department of Neurology, University Hospital of Bellvitge, Barcelona, Spain
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  • Teresa Ribalta MD

    1. Neurological Tissue Bank of the Biobanc-Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
    2. Department of Pathology, Hospital Clínic de Barcelona, Barcelona, Spain
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  • Funding agencies: This study has been performed with the financial support of the Beca de Recerca Clínica de l'Acadèmia de Ciències Mèdiques 2011, the “Distinció per la promoció de la Recerca Universitaria Generalitat de Catalunya” to E.T. (2001SRG00387 Generalitat de Catalunya), and the Spanish network on neurodegenerative diseases CIBERNED. E.G. is partially funded by the Spanish Ministry “Ministerio de Economía y Competitividad, PTA 2011.” J.N.-O. holds a predoctoral grant from IDIBAPS “Beques formació personal investigador IDIBAPS.”

  • Relevant conflicts of interest/financial disclosures: E.G. received a research grant from “Academia de Ciències Mèdiques de Catalunya, Beca de Recerca Clínica 2011” and is partially supported by the Spanish ministry Ministerio de Economía y Competitividad, programa PTA 2011. J.N.-O. was supported by a grant “Premio Fin de Residencia Emili Letang” from Hospital Clinic, Barcelona, Spain, by a research grant from “Acadèmia de Ciencies Mèdiques de Catalunya, Beca de Recerca Clínica 2011” and is supported by a research grant from Institut d'Investigacions Biomèdiques August Pi i Sunyer. E.T. received the “Distinció per la promoció de la Recerca Universitaria Generalitat de Catalunya” (2001SRG00387 Generalitat de Catalunya), and support from the Spanish network on neurodegenerative diseases CIBERNED.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Lewy body (LB) diseases are characterized by alpha-synuclein (AS) aggregates in the central nervous system (CNS). Involvement of the peripheral autonomic nervous system (pANS) is increasingly recognized, although less studied. The aim of this study was to systematically analyze the distribution and severity of AS pathology in the CNS and pANS. Detailed postmortem histopathological study of brain and peripheral tissues from 28 brain bank donors (10 with Parkinson's disease [PD], 5 with dementia with LB [DLB], and 13 with non-LB diseases including atypical parkinsonism and non-LB dementia). AS aggregates were found in the pANS of all 15 LB disease cases (PD, DLB) in stellate and sympathetic ganglia (100%), vagus nerve (86.7%), gastrointestinal tract (86.7%), adrenal gland and/or surrounding fat (53.3%), heart (100%), and genitourinary tract (13.3%), as well as in 1 case of incidental Lewy body disease (iLBD). A craniocaudal gradient of AS burden in sympathetic chain and gastrointestinal tract was observed. DLB cases showed higher amounts of CNS AS aggregates than PD cases, but this was not the case in the pANS. No pANS AS aggregates were detected in Alzheimer's disease (AD) cases with or without CNS AS aggregates. All pathologically confirmed LB disease cases including 1 case of iLBD had AS aggregates in the pANS with a craniocaudal gradient of pathology burden in sympathetic chain and gastrointestinal tract. AS was not detected in the pANS of any AD case. These findings may help in the search of peripheral AS aggregates in vivo for the early diagnosis of PD. © 2014 International Parkinson and Movement Disorder Society

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