A MyParkinsonsTeam member recently asked, “Should I do genetic testing for PD? Several of my family members have had it … Does it run in families?”
The short answer is: it’s complicated. There is still much that scientists do not know about Parkinson’s disease (PD). It remains largely unknown why certain people get it and others don’t. Based on the available data and research, most scientists believe that Parkinson’s is due to a combination of nature and nurture — genetics plus environmental factors. These factors may include certain drugs or exposures to chemicals like pesticides and herbicides.
About 85 percent of Parkinson’s cases are thought to be sporadic, meaning they occur without any genetic factors that can be identified. The other 15 percent of cases are considered potentially familial or genetic, with certain genes and mutations leading to an increased risk of developing Parkinson’s.
If you know of family members who have Parkinson’s, you may be wondering if you or others will get it one day as well. Therefore, it’s important to understand a few key facts about what might prompt Parkinson’s to develop.
Much of today’s mainstream understanding of Parkinson’s disease is based on a substance called dopamine. It is one of many molecules called neurotransmitters that brain cells and nerve cells (neurons) use to talk to one another. The right balance of dopamine and other neurotransmitters causes people’s brains (and the rest of the nervous system) to work so they can control movements properly.
Parkinson’s has long been thought to be due to low levels of dopamine being made by special dopamine-producing cells in a part of the brain called the substantia nigra — either because something causes these cells to die or it blocks the effects of dopamine. This lower dopamine activity then causes the classic symptoms of Parkinson’s like slow movements (bradykinesia) or shaking (tremors). It also explains why forms of dopamine, and other drugs that increase its level, are given as medication for people with Parkinson’s — for example, levodopa/carbidopa (sold under the brand names Sinemet, Parcopa, and Rytary).
Alpha-synuclein is a protein produced in nerve cells, and it normally does not cause significant issues. It gets made and can easily be cleared out of neurons. However, when the structure of the protein is changed through a genetic mutation, the abnormal form of alpha-synuclein folds in on itself, bunches up, and accumulates in heaps called Lewy bodies. These cannot be cleaned up by the cell, and the buildup results in damage over time. This damage to the substantia nigra and dopamine-producing neurons can lead to the development of parkinsonism.
Several genes have been identified in genetic testing of people with Parkinson’s and laboratory animals who have developed Parkinson’s. Currently, researchers that are testing new Parkinson’s drugs that target specific gene mutations.
Many genes involved in Parkinson’s disease are inherited in either autosomal dominant or autosomal recessive patterns. Everyone has two copies of each gene (a section of the DNA that codes for a certain molecule byproduct) within their genome (their entire DNA). Each parent passes one of these copies onto their children, with the other coming from the other parent.
Dominant traits require that only one copy of a genetic mutation is inherited, which can be from either parent. Recessive traits, on the other hand, require two copies of a mutation — one from each parent.
Parkin (PRKN or Park2 gene) is a protein that is part of the repair system when a portion of the cell called mitochondria — the energy-producing center of cells — becomes damaged. It also helps cells clear waste and extra unnecessary proteins. Mutations to the Parkin gene, therefore, cause cells to fail to repair damage and die as a result.
Pink1 has a very similar function to parkin in the mitochondria, protecting them from malfunctioning during periods of cellular stress, such as unusually high energy demands.
Park7 is a gene that codes for a protein (DJ-1) that is a damage sensor against dangerous atoms called free radicals — it helps sense when a cell is under too much stress from these radicals and helps respond appropriately. Mutations to Park7 disrupt this process and cause dopamine-producing cells to cave under stress and die.
SNCA is the gene that encodes alpha-synuclein. A mutation in this gene may alter the structure of alpha-synuclein enough so that it is more prone to clumping together and accumulating to toxic levels in dopamine-producing brain cells.
LRRK2 codes for a protein called dardarin, which can recycle proteins (like alpha-synuclein) in the cell for other uses, helps to determine which proteins are made by the cell, and helps maintain the cell’s skeleton.
Interestingly, LRRK2 is not just found in the brain but also in many other organs and cell types, such as heart cells, blood cells, and immune cells.
The GBA gene represents a protein called glucocerebrosidase, which breaks down certain types of fatty waste molecules that build up within brain cells. Mutations to GBA mean that cells fail to break down these waste products, causing them to accumulate and kill the brain cell.
GBA mutations are found in many cases of Parkinson’s disease when people experience early motor signs (such as tremor) compared to the general population of people with Parkinson’s overall.
Like any other condition, there are risk factors for Parkinson’s disease. Age and genetic history are two of the most common factors that may increase disease risk. In sporadic cases, genetics are not a major factor, and so those who get sporadic Parkinson’s are often much older when they are diagnosed and start noticing symptoms. Genetic forms usually have a family history — for example, maybe a parent or grandparent developed Parkinson’s.
Don’t hesitate to discuss your family’s medical history with your doctor, as this can add depth to the medical advice you receive from your health care team.
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