Lewy body pathology involves cutaneous nerves

J Neuropathol Exp Neurol. 2008 Oct;67(10):945-53. doi: 10.1097/NEN.0b013e318186de48.


Involvement of the peripheral autonomic nervous system is a core feature of Lewy body (LB) diseases, including Parkinson disease (PD), PD with dementia, and dementia with LBs. To investigate the potential use of skin biopsy for the diagnosis of LB diseases, we assessed anti-phosphorylated alpha-synuclein immunoreactivity in peripheral nerves in samples of skin from the abdominal wall and flexor surface of the upper arm in 279 prospectively studied consecutively autopsied patients whose data were registered at the Brain Bank for Aging Research between 2002 and 2005. Positive immunoreactivity was demonstrated in the unmyelinated fibers of the dermis in 20 of 85 patients with LB pathology in the CNS and the adrenal glands, the latter representing a substitute for peripheral autonomic nervous system sympathetic ganglia; no reactivity was seen in 194 patients without CNS LB pathology. In 142 retrospectively studied patients autopsied from 1995 onward who had subclinical or clinical LB disease, the sensitivity of the positive skin immunoreactivity was 70% in PD and PD with dementia and 40% in dementia with LBs. Skin immunoreactivity was absent in cases of multiple-system atrophy, progressive nuclear palsy, and corticobasal degeneration. We demonstrate for the first time that the skin is involved and may be a highly specific and useful biopsy site for the pathological diagnosis of LB diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / pathology
  • Aged
  • Aged, 80 and over
  • Aging / pathology
  • Autonomic Nervous System Diseases / pathology
  • Autopsy
  • Central Nervous System / pathology
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Lewy Bodies / pathology*
  • Male
  • Microscopy, Immunoelectron
  • Middle Aged
  • Paraffin Embedding
  • Skin / innervation*
  • Skin / pathology*
  • alpha-Synuclein / metabolism


  • alpha-Synuclein