Where does parkinson disease pathology begin in the brain?

J Neuropathol Exp Neurol. 2002 May;61(5):413-26. doi: 10.1093/jnen/61.5.413.


The substantia nigra is not the induction site in the brain of the neurodegenerative process underlying Parkinson disease (PD). Instead, the results of this semi-quantitative study of 30 autopsy cases with incidental Lewy body pathology indicate that PD in the brain commences with the formation of the very first immunoreactive Lewy neurites and Lewy bodies in non-catecholaminergic neurons of the dorsal glossopharyngeus-vagus complex, in projection neurons of the intermediate reticular zone, and in specific nerve cell types of the gain setting system (coeruleus-subcoeruleus complex, caudal raphe nuclei, gigantocellular reticular nucleus), olfactory bulb, olfactory tract, and/or anterior olfactory nucleus in the absence of nigral involvement. The topographical parcellation of the nuclear grays described here is based upon known architectonic analyses of the human brainstem and takes into consideration the pigmentation properties of a few highly susceptible nerve cell types involved in PD. In this sample and in all 58 age- and gender-matched controls, Lewy bodies and Lewy neurites do not occur in any of the known prosencephalic predilection sites (i.e. hippocampal formation, temporal mesocortex, proneocortical cingulate areas, amygdala, basal nucleus of Meynert, interstitial nucleus of the diagonal band of Broca, hypothalamic tuberomamillary nucleus).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Glossopharyngeal Nerve / pathology*
  • Humans
  • Lewy Bodies / chemistry
  • Lewy Bodies / pathology
  • Locus Coeruleus / pathology*
  • Male
  • Nerve Tissue Proteins / analysis
  • Olfactory Bulb / pathology*
  • Olfactory Pathways / pathology
  • Parkinson Disease / pathology*
  • Raphe Nuclei / pathology
  • Reticular Formation / pathology
  • Substantia Nigra / pathology
  • Synucleins
  • Vagus Nerve / pathology*


  • Nerve Tissue Proteins
  • Synucleins