The progression of pathology in Parkinson's disease.
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.
Halliday
Glenda Margaret
GM
Prince of Wales Medical Research Institute and University of New South Wales, Sydney, Australia. g.halliday@powmri.edu.au
McCann
Heather
H
D001344:Autopsy; D003704:Dementia / Q000209:etiology / Q000473:pathology; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D008137:Longitudinal Studies; D008636:Mesencephalon / Q000473:pathology; D009474:Neurons / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D051844:alpha-Synuclein / Q000378:metabolism
D051844:alpha-Synuclein; D004298:Dopamine