The progression of pathology in Parkinson's disease

Abstract

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 α‐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.