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Time Course of Neuron Loss in Parkinsonís Disease
- Sep 17 2013
For the first time, researchers have estimated in detail the pace at which certain brain cells are lost to Parkinson’s disease (PD) during its progression. They report their results in the August 2013 issue of Brain.
Parkinson’s is a progressive neurological disease that results from the gradual loss of brain cells that produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. As Parkinson's progresses, dopamine in the brain decreases, leaving a person unable to control movement normally.
To better understand these brain changes, researchers led by Jeffrey Kordower, Ph.D., at the PDF Research Center at Rush University Medical Center studied how certain areas of the brain change after PD diagnosis. They examined brain tissue taken from 28 people who died between one and 27 years after a PD diagnosis.
Researchers compared this tissue to brain tissue from elderly people without PD. The tissue sections were taken from two areas of the brain: the substantia nigra (SNc), where dopamine neurons live, and the brain area where these neurons release their dopamine—called the striatum or, more precisely, the putamen. Dr. Kordower and his colleagues counted the number of healthy neurons in the brain tissue.
- When studying brain tissue of people who had died at the earliest time (one to seven years) after a PD diagnosis, researchers found 50–90 percent fewer healthy dopaminergic neurons in the SNc than in brain tissue from people without PD.
- Brain tissue from those who died after many years of living with PD only showed slightly greater neuron loss than tissue of those who had died in the early stages of PD.
- When researchers examined the brain of one person who died within one year from diagnosis, they looked for another specific type of neuron that contains melanin. The SNc showed loss of only 10 percent of this type of neuron.
- Among those who had died after four to five years of living with Parkinson's, 30–60 percent of their total dopamine-producing neurons had been lost.
- When examining the putamen, among people who had died one to three years after PD diagnosis, 35–75 percent of healthy dopaminergic fibers were lost. Among those with five years disease duration, 70–90 percent had been lost, with little change after that.
What Does It Mean?
A key finding of this study is that the people who lived with PD had generally lost most of their healthy dopamine-producing neurons, even within just four years of PD diagnosis. This indicates that the majority of neuron loss may occur early on in the course of Parkinson's disease.
While this result appears solid, further study is needed to confirm it. For example, since there was only one brain available from someone who had been diagnosed with PD for only a year, researchers would need to study others who died in the early stages of PD.
These results suggest that therapies that seek to reverse or stop PD may be likely to succeed at early stages of PD, when many healthy dopamine-producing neurons remain. It also suggests clinical studies testing new potential therapies for PD may see the best effect when targeted to people within the first four years of their PD diagnosis. In turn, the results emphasize the need to better detect PD at the earliest stages possible.
Another important result was that most people with PD seemed to lose melanin-containing dopamine-producing neurons at a slower and more variable pace. This finding provides hope that there are remaining dopamine-producing neurons, which could potentially be restored, or made healthy, with treatment. For example, even 27 years after PD diagnosis, the scientists still found evidence of a small pool of neurons that might still be able to respond to future neurorestorative therapies.
Researchers were able to conduct this study due to the generous contributions of people with PD who donated their brains to science. Learn more about brain donation by reading a personal story from PDF Research Advocate Diana Barnwell, or browsing a list of brain banks around the US.
Reference: Kordower JH, Olanow CW, Dodiya HB, Chu Y, Beach TG, Adler CH, Halliday GM, Bartus RT (2013) Disease duration and the integrity of the nigrostriatal system in Parkinson's disease. Brain 136:2419–2431. DOI: 10.1093/brain/awt192 http://dx.doi.org/10.1093/brain/awt192
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Source Date: Sep 17 2013