Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies

Am J Pathol. 1998 Apr;152(4):879-84.


Lewy bodies (LBs) are hallmark lesions of degenerating neurons in the brains of patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recently, a point mutation in the gene encoding the presynaptic alpha-synuclein protein was identified in some autosomal-dominantly inherited familial PD pedigrees, and light microscopic studies demonstrated alpha-synuclein immunoreactivity in LBs of sporadic PD and DLB. To characterize alpha-synuclein in LBs, we raised monoclonal antibodies (MAbs) to LBs purified from DLB brains and obtained a MAb specific for alpha-synuclein that intensely labeled LBs. Light and electron microscopic immunocytochemical studies performed with this MAb as well as other antibodies to alpha-and beta-synuclein showed that alpha-synuclein, but not beta-synuclein, is a component of LBs in sporadic PD and DLB. Western blot analyses of highly purified LBs from DLB brains showed that full-length as well as partially truncated and insoluble aggregates of alpha-synuclein are deposited in LBs. Thus, these data strongly implicate alpha-synuclein in the formation of LBs and the selective degeneration of neurons in sporadic PD and DLB.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal / analysis
  • Blotting, Western
  • Brain / metabolism
  • Brain Stem / metabolism
  • Dementia / metabolism*
  • Humans
  • Immunohistochemistry
  • Lewy Bodies / metabolism*
  • Microscopy, Immunoelectron
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / metabolism*
  • Parkinson Disease / metabolism*
  • Synucleins
  • Ubiquitins / metabolism
  • alpha-Synuclein
  • beta-Synuclein


  • Antibodies, Monoclonal
  • Nerve Tissue Proteins
  • SNCA protein, human
  • SNCB protein, human
  • Synucleins
  • Ubiquitins
  • alpha-Synuclein
  • beta-Synuclein