Figuring out what happens first in Parkinson’s disease is a difficult task. People are not usually diagnosed until they experience motor symptoms, at which point 70-80% of their nigrostriatal dopamine neurons have already died. This makes it hard to trace the sequence of events that leads to neuronal degeneration.
This seems like an odd question given that only a small percentage of people actually get Parkinson’s disease. Nevertheless, the question has always perplexed me. Here’s my rationale. The main neurons responsible for the motor symptoms of Parkinson’s disease are dopamine-containing cells that project from the substantia nigra pars compacta to the striatum. In the striatum, each nigrostriatal dopamine neuron branches into a dizzying array of tiny appendages that make hundreds of thousands of synapses.1, 2 And these neurons do…