Chapter 16 - Pathology in Parkinson’s Disease

Summary

Parkinson’s disease has been recently redefined clinically and its underlying molecular biology determined. Although it is a neurodegenerative disease, loss of neurons is largely focal rather than large scale; symptoms are caused more by neurochemical deficits and dysfunctional cells than cell loss. The two main pathologic features are loss of dopamine neurons in the substantia nigra of the midbrain and the more widespread aggregation of a-synuclein in certain vulnerable neurons in the brain. Several triggers can cause the molecular cascade that kills dopamine neurons and makes the a-synuclein protein fibrilize and aggregate initially in brainstem neurons, including genetic variants and post-translational modification of the protein. The disease is slowly progressive with the propagation of aggregates from vulnerable synapses to the entire neuron, then from one neuron to other neurons and glial cells. Different propagation mechanisms have been identified for these different brain cells that work in concert to sustain the slow disease process. Current therapeutic delivery of dopamine or deep brain stimulation temporarily relieve the symptoms with disease-modifying treatments now able to be trialled due to identifying the underlying molecular biology.