The key pathology in Parkinson’s Disease (PD) is α-synuclein accumulation. Large α-synuclein aggregates form round lamellate eosinophilic cytoplasmic inclusions, Lewy bodies (LBs) in the neuronal body. α-synuclein is toxic. Its accumulation impairs the functions of the cell. The core pathology of PD affects the dopamine-producing neurons of the substantia Nigra (SN). In advanced PD, loss of pigmented neurons results in gross depigmentation of the SN.
The triad of rigidity, bradykinesia and tremor at rest correlates with degeneration of the dopaminergic nigrostriatal pathway and dopamine depletion in the striatum. α-synuclein deposits and LBs are also present in the cerebral cortex, limbic system and in many extra-nigral neuronal groups. This is the underlying pathology for PD.