Olfactory pathogenesis of idiopathic Parkinson disease revisited

Mov Disord. 2008 Jun 15;23(8):1076-84. doi: 10.1002/mds.22066.


Idiopathic Parkinson disease (PD) is traditionally considered a movement disorder with hallmark lesions located in the substantia nigra pars compacta (SNpc). However, recent histopathological studies of some PD cases suggest the possibility of a multisystem disorder which progresses in a predictable sequence as described in Braak's staging criteria. The disease process starts in the dorsal motor nucleus of the vagus (dmX) and anterior olfactory nucleus and bulb, and from there, spreads through the brainstem nuclei to ultimately reach the SNpc, which then presents as symptomatic PD. In this article, we would like to revisit the olfactory pathogenesis of PD based on Braak's staging system and review anatomical pathways supporting such a possibility. We also suggest some biomarkers for early stages of PD. Additionally, we present and discuss the possibility that a prion-like process underlies the neurodegenerative changes in PD.

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Brain Stem / pathology*
  • Cerebral Cortex / pathology
  • Humans
  • Lewy Bodies / pathology
  • Limbic System / pathology
  • Nerve Degeneration / diagnosis
  • Nerve Degeneration / pathology*
  • Neural Pathways / pathology
  • Neurons / pathology
  • Olfactory Bulb / pathology*
  • Olfactory Nerve / pathology*
  • Parkinson Disease / diagnosis
  • Parkinson Disease / pathology*
  • Prion Diseases / diagnosis
  • Prion Diseases / pathology*
  • Substantia Nigra / pathology*
  • Vagus Nerve / pathology
  • Vagus Nerve Diseases / diagnosis
  • Vagus Nerve Diseases / pathology*
  • alpha-Synuclein / metabolism


  • Amyloid beta-Peptides
  • alpha-Synuclein