- Parkinson disease (PD) is a heterogeneous movement disorder caused by progressive neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the midbrain.
- Clinical diagnosis requires presence of motor parkinsonism — bradykinesia plus rest tremor and/or rigidity — in the presence of other supportive criteria (e.g., symptomatic improvement with dopaminergic therapy) .
- Neuropathological confirmation of hallmark features is required for definitive diagnosis (i.e., loss of pigmented dopamine neurons in the SNpc and neuronal Lewy body inclusions composed of α-synuclein, ubiquitin, and other aggregated proteins).
- Both cell autonomous (e.g., neuronal mitochondrial dysfunction) and non-cell autonomous (e.g., inflammation, protein aggregate spread) mechanisms have been described and may contribute variably to the heterogeneity of PD .
- Motor signs of disease do not appear until about 2/3 of the dopamine neurons of the SNpc have degenerated, suggesting a motorically “silent” prodromal phase with profound compensation .
- PD pathology affects other neurotransmitter systems and brain areas, such as the noradrenergic locus coeruleus, cholinergic basal forebrain, and serotonergic raphe nuclei, which may be important for understanding the variegated set of motor, non-motor, and neuropsychiatric phenomena experienced by PD patients.
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