It took almost 100 years before a meaningful advance occurred in any basic 
science understanding of Parkinson disease (PD) following James Parkinson's 
description in 1817. The Lewy body was described in 1912, and the substantia 
nigra was found to be depigmented with neuronal loss and gliosis in 1919. The 
link between dopamine and PD began in 1957, 140 years after Parkinson's Essay. 
Arvid Carlsson and Oleh Hornykiewicz were the major pioneers. The revolutionary 
therapeutic breakthrough was the introduction of high dosage levodopa therapy by 
George Cotzias in 1967. Following 40 years of the dopa/dopamine era, we have 
entered the era of alpha-synuclein, the protein present in Lewy bodies. Heiko 
Braak found that alpha-synuclein accumulates initially in the olfactory system 
and lower brainstem and then travels in an anatomic pattern to involve other 
regions of the brain and thereby cause progressive symptoms. Alpha-synuclein was 
somehow converted to a rogue protein. Where this originates and how it is 
propagated are under intense investigation. At the same time that the 
alpha-synuclein era was developing, clinical advances took place by recognizing 
PD as hosting a wide variety of nonmotor features with eventual cognitive 
impairment in many. Therapeutics has also evolved. Although the most effective 
therapy for the motor features remains levodopa, surgical approaches and drugs 
for nonmotor problems continue to expand our ability to treat people with PD. We 
can expect therapeutic advances in neuroprotection as the basic science 
discoveries uncovered in the alpha-synuclein era are translated into effective 
treatments.