One major challenge in treating Parkinson's disease (PD) is that no one can predict how the disease will manifest in different people. No two people with Parkinson's seem to experience the exact same symptoms, age of onset, rate of progression and even treatment response. Genetics may help explain some of these differences.

Scientists have identified mutations (or changes) in several genes associated with Parkinson's. However, certain mutations seem to be more common than others.

These gene mutations change the role a protein plays and influences the risk for developing Parkinson's (read Understanding Genetics to learn more). Not all people with gene mutations develop Parkinson's and by understanding different inherited genetic backgrounds of people with Parkinson's, we can begin to understand what causes some people to develop certain symptoms while others do not.

Below are the most common mutations in genes that are associated with Parkinson's. Each mutation interrupts a protein from its normal workload, increasing the risk of developing Parkinson's:

• LRRK2. Genetic changes in this gene can be found in up to 2% of all people with PD. Certain ethnic groups like Ashkenazi Jews, North African Arab Berber and Basque populations have a higher prevalence (about 30%) of Parkinson's than the general population. As Parkinson's is a neurodegenerative disorder, having a mutation in this gene ultimately results in the loss of neurons. There are at least 20 different PD-associated mutations that could occur in this gene, some are more common, like G2019S. Pharmaceutical companies are currently testing drugs that block the abnormal activity of this gene to treat Parkinson's.
• GBA. Between 5 to 10% of people with Parkinson's have a mutation in this gene. The chances that those who carry this mutation will develop Parkinson's in the future is fairly low. Scientists have identified more than 380 mutations in this gene, and only a handful have been linked to increased risk for Parkinson's. The GBA1 gene produces a protein responsible for managing the cell's garbage disposal system called GCase (glucocerebrosidase). Mutations in GBA1 are ultimately linked to the build-up of alpha-synuclein clumps. Pharmaceutical companies are currently testing drugs that target this gene to help improve the efficiency of the garbage disposal system to help slow or stop the progression of Parkinson's.
• SNCA. This gene produces the protein alpha-synuclein. Genetic changes in this gene can produce excess alpha-synuclein, which accumulates abnormally in the brains of people with Parkinson's and is toxic. Lewy bodies are made up of clumps of alpha-synuclein protein and are found in brains of all people with Parkinson's. Researchers are working to design treatments that can reduce levels of toxic alpha-synuclein clumps in people with Parkinson's. In 1997, Parkinson's Foundation research fellow Roger Duvoisin, MD, was the first person to identify SNCA as the first PD gene.

Genetic research has made great strides to help scientists better understand the biology of Parkinson's and guide the development of treatments for all people with PD. In the near future, knowing a person's genetic background may help predict the most effective treatments.

Ongoing work, like the PD GENEration study, will uncover more details about how genetic factors play a role in Parkinson's, helping us better understand this complex disease.