About 100 people have a rare mutation in a gene called SNCA that puts them at almost certain risk of contracting Parkinson's disease. This makes them ideal subjects to study the causes of this debilitating condition. Most of these people live in northern Peloponnese, Greece, and a handful lives in Campania, Italy. We were fortunate to have 14 of these people agreeing to travel to London so we could study their brains.
More than 6 million people globally have Parkinson's disease; is the second most common neurodegenerative disorder after Alzheimer's disease.
Symptoms, which worsen over time, include motor symptoms such as stiffness, sluggishness, and tremor, as well as non-motor symptoms such as memory problems. Researchers have been trying to find a reliable marker for the disease so people at risk can be identified before the onset of motor symptoms.
There are no cures for Parkinson's disease, but symptoms are treated with drugs that restore the brain's chemical substance called dopamine to normal levels. Dopamine has been considered a major culprit in Parkinson's disease because low levels cause problems with movement. But another brain chemical called serotonin has also been implicated in the disease.
But we do not know how early and to what extent changes in serotonin occur and whether these changes are related to the onset of the disease. To help answer this, we needed to study Greek and Italian individuals with the mutation of the SNCA gene.
Studying these gene carriers before they develop Parkinson's disease is a unique opportunity to understand what comes first in the cascade of events that eventually leads to the diagnosis of Parkinson's disease. This knowledge is fundamental so that we can develop sensitive markers to track the progression of the disease.
People with the mutation tend to have symptoms of Parkinson's disease in their 40s or 50s, so we wanted to study individuals in the 20s and 30s to see if there was any change in the brain a decade or more before the symptoms started.
Seven of our volunteers, who kindly visited our laboratory for ten days of brain imaging and neurological tests, had no motor symptoms and seven were diagnosed with Parkinson's disease.
We also examined 25 patients with sporadic Parkinson's disease (Parkinson's disease without a genetic cause) and 25 healthy volunteers.
All participants had three brain exams: one to measure dopamine, one to measure serotonin, and one to study anatomical regions in the brain.
We also conducted a series of clinical trials to investigate motor and non-motor symptoms. The volunteers used an electronic device on their wrist for seven days to detect any movement associated with Parkinson's disease – a move that may be too subtle to be detected by a neurologist with the naked eye.
These tests confirmed that the seven individuals with the genetic mutation who did not have motor symptoms were, in fact, Parkinson's free.
Early loss of serotonin
Comparison of data from the different groups allowed us to measure the severity of the loss of dopamine and serotonin at different stages of the disease, from symptomless to diagnosed.
It also allowed us to compare the changes observed in gene carriers with the changes observed in those with sporadic Parkinson's disease. This has helped us translate our findings into gene carriers into the more common sporadic form of Parkinson's disease.
We found that carriers of genes without symptoms had depleted serotonin, while their dopamine neurons seemed to remain intact. Therefore, the changes in the serotonin system we identify will probably begin very early and precede the onset of motor symptoms for a few years.
Our study, published in Lancet Neurology, suggests that changes in the serotonin system come first, occurring many years before patients experience symptoms. This important finding could lead to the development of new drugs to delay or even prevent the progression of the disease.
Our findings also suggest that the brain scans of the serotonin system could be used as a tool for screening and monitoring the progression of the disease. But these scans are expensive, so we need more work to develop affordable technology.
We also need more research on the genetic forms of Parkinson's disease, which could reveal the first changes underlying this terrible disease.
Heather Wilson, associate researcher, King's College London and Marios Politis, Lily Safra Professor of Neurology and Neuroimaging, King's College London.
This article was republished in The Conversation under a Creative Commons license. Read the original article.