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Multi-organ distribution of phosphorylated α-synuclein histopathology in subjects with Lewy body disorders

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Arizona Parkinson’s Disease Consortium, Beach, Thomas G., Adler, Charles H., Sue, Lucia I., Vedders, Linda, Lue, LihFen, White III, Charles L., Akiyama, Haru +4 more·2010·Acta Neuropathologica
DOI 10.1007/s00401-010-0664-3PMC PMC2866090
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Abstract

A sensitive immunohistochemical method for phosphorylated alpha-synuclein was used to stain sets of sections of spinal cord and tissue from 41 different sites in the bodies of 92 subjects, including 23 normal elderly, 7 with incidental Lewy body disease (ILBD), 17 with Parkinson's disease (PD), 9 with dementia with Lewy bodies (DLB), 19 with Alzheimer's disease with Lewy bodies (ADLB) and 17 with Alzheimer's disease with no Lewy bodies (ADNLB). The relative densities and frequencies of occurrence of phosphorylated alpha-synuclein histopathology (PASH) were tabulated and correlated with diagnostic category. The greatest densities and frequencies of PASH occurred in the spinal cord, followed by the paraspinal sympathetic ganglia, the vagus nerve, the gastrointestinal tract and endocrine organs. The frequency of PASH within other organs and tissue types was much lower. Spinal cord and peripheral PASH was most common in subjects with PD and DLB, where it appears likely that it is universally widespread. Subjects with ILBD had lesser densities of PASH within all regions, but had frequent involvement of the spinal cord and paraspinal sympathetic ganglia, with less-frequent involvement of end-organs. Subjects with ADLB had infrequent involvement of the spinal cord and paraspinal sympathetic ganglia with rare involvement of end-organs. Within the gastrointestinal tract, there was a rostrocaudal gradient of decreasing PASH frequency and density, with the lower esophagus and submandibular gland having the greatest involvement and the colon and rectum the lowest.

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  • A large study by the Arizona Parkinson's consortium group did not find a single case in which α-synuclein was present in the enteric nervous system but not in the central nervous system in a survey of whole-body autopsies from individuals with Lewy body disorders (including PD) and matched controls.

    “Despite this, a large study by the Arizona Parkinson’s consortium group did not find a single case in which α-synuclein was present in the enteric nervous system but not in the central nervous system in a survey of whole-body autopsies from individuals with Lewy body disorders (including PD) and matched controls [63].”

    From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [63]

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Authors
Arizona Parkinson’s Disease Consortium, Beach, T. G., Adler, C. H., Sue, L. I., Vedders, L., Lue, L., White III, C. L., Akiyama, H., Caviness, J. N., Shill, H. A., Sabbagh, M. N., & Walker, D. G.
Affiliations
  • Banner Sun Health Research Institute (US)
  • Mayo Clinic (US)
  • Tokyo Institute of Psychiatry (JP)
Corresponding author
Beach, Thomas G.
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2010-03-21
Volume
119
Issue
6
Pages
689-702
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-010-0664-3
PMC
PMC2866090
OpenAlex
W2085022353
Cited by
911
References
5
Citations by year
2026: 39 · 2025: 52 · 2024: 55 · 2023: 62 · 2022: 75 · 2021: 99 · 2020: 62 · 2019: 68 · 2018: 66 · 2017: 55 · 2016: 57 · 2015: 56 · 2014: 52 · 2013: 40 · 2012: 37
FWCI
21.38
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Acta Neuropathologica (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Japan Society for the Promotion of Science (21591536)
  • National Institute on Aging (P30-AG-19610, P30AG019610)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
phosphorylated alpha-synuclein, Lewy body disease, Parkinson's disease, dementia with Lewy bodies, incidental Lewy body disease, spinal cord, vagus nerve, gastrointestinal tract, endocrine organs, immunohistochemistry
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Ganglia, Sympathetic, Humans, Immunohistochemistry, Male, Parkinson Disease, Phosphorylation, Spinal Cord, Peripheral Nervous System, Lewy Body Disease, Gastrointestinal Tract, alpha-Synuclein

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