The progression of pathology in Parkinson's disease

Ann N Y Acad Sci. 2010 Jan;1184:188-95. doi: 10.1111/j.1749-6632.2009.05118.x.


To identify the progression of pathology over the entire course of Parkinson's disease, we longitudinally followed a clinical cohort to autopsy and identified three clinicopathological phenotypes that progress at different rates. Typical Parkinson's disease has an initial rapid loss of midbrain dopamine neurons with a slow progression of Lewy body infiltration into the brain (over decades). Dementia intervenes late when Lewy bodies invade the neocortex. Older onset patients (> 70 years old) dement earlier and have much shorter disease durations. Paradoxically, they have far more alpha-synuclein-containing Lewy bodies throughout the brain, and many also have additional age-related plaque pathology. In contrast, dementia with Lewy bodies has the shortest disease course, with substantive amounts of Lewy bodies and Alzheimer-type pathologies infiltrating the brain. These data suggest that two age-related factors influence pathological progression in Parkinson's disease--the age at symptom onset and the degree and type of age-related Alzheimer-type pathology.

Publication types

  • Review

MeSH terms

  • Autopsy
  • Dementia / etiology
  • Dementia / pathology
  • Disease Progression
  • Dopamine / metabolism
  • Humans
  • Lewy Bodies / pathology
  • Longitudinal Studies
  • Mesencephalon / pathology
  • Neurons / pathology
  • Parkinson Disease / genetics
  • Parkinson Disease / pathology*
  • Parkinson Disease / physiopathology
  • Phenotype
  • alpha-Synuclein / metabolism


  • alpha-Synuclein
  • Dopamine