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

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Abstract

A sensitive immunohistochemical method for phosphorylated α-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 α-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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Acknowledgments

This research is supported by Grants to the Sun Health Research Institute Brain and Body Donation Program and the Arizona Parkinson’s Disease Consortium by the Michael J. Fox Foundation for Parkinson’s Research (The Prescott Family Initiative), the Arizona Biomedical Research Commission (contracts 4001, 0011 and 05-901) and the National Institute on Aging (Arizona Alzheimer’s Disease Consortium, P30 AG19610). We would like to thank other members of the Arizona Parkinson’s Disease Consortium, including Erika Driver-Dunckley, MD, Virgilio Evidente, MD, and Donald Connor, PhD.

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  1. Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ, 85351, USA

    Thomas G. Beach, Lucia I. Sue, Linda Vedders, LihFen Lue, Holly A. Shill, Marwan N. Sabbagh & Douglas G. Walker

  2. Mayo Clinic, Scottsdale, AZ, USA

    Charles H. Adler & John N. Caviness

  3. University of Texas Southwestern Medical Center, Dallas, TX, USA

    Charles L. White III

  4. Tokyo Institute of Psychiatry, Tokyo, Japan

    Haru Akiyama

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Beach, T.G., Adler, C.H., Sue, L.I. et al. Multi-organ distribution of phosphorylated α-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 119, 689–702 (2010). https://doi.org/10.1007/s00401-010-0664-3

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