Parkinson's Disease Overview
Neuronal Pathways that Degenerate in Parkinson's Disease.
National Human Genome Research Institute
Parkinson’s disease (PD) is a neurological condition that typically causes tremor and/or stiffness in movement. The condition affects about 1 to 2 percent of people over the age of 60 years and the chance of developing PD increases as we age. Most people affected with PD are not aware of any relatives with the condition but in a number of families, there is a family history. When three or more people are affected in a family, especially if they are diagnosed at an early age (under 50 years) we suspect that there may be a gene making this family more likely to develop the condition.
Genetics: The Basics
Our genetic material is stored in the center of every cell in our bodies (skin cells, hair cells, blood cells). This genetic material comes in individual units called genes. We all have thousands of genes. Genes carry the information the body needs to make proteins, which are the substances in the body that actually carry out all the functions we need to live and grow. Our genes affect many things about us: our height, eye color, why we respond to some medications better than others and our likelihood of developing certain conditions. We have two copies of every gene: we inherit one copy, one member of each pair, from our mother and the other from our father. We then pass only one copy of a gene from each pair of genes to the next generation. Whether we pass on the gene we got from our father or the one from our mother is purely by chance, like flipping a coin heads or tails.
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We all have genes that don’t work properly. In most cases the other copy of the gene makes up for the one that does not work properly and we are healthy. A problem only arises if we meet someone else who has a non-working copy of the same gene and we have a child who inherits two non-working copies of that gene. This is called recessive inheritance.
Sometimes if one of our genes is not working properly the other copy of the gene cannot make up for it and that causes a condition or an increased risk of developing a condition. Each time we have a child we randomly pass on one copy of each gene. If the child inherits the copy that doesn’t work properly, they too may develop the condition. This is called dominant inheritance.
What genes are linked to Parkinson’s disease?
In 1997, we studied a large family that came from a small town in Southern Italy in which PD was inherited from parent to child (dominant inheritance). We found the gene that caused their inherited Parkinson’s Disease and it coded for a protein called alpha-synuclein. If one studies the brains of people with PD after they die, one can see tiny little accumulations of protein called Lewy Bodies (named after the doctor who first found them). Research has shown that there is a large amount of alpha-synuclein protein in the Lewy Bodies of people who have non-inherited PD as well as in the brains of people who have inherited PD. This immediately told us that alpha-synuclein played an important role in all forms of PD and we are still doing a lot of research to better understand this role.
Since 1997 four other genes have been found and they have been named parkin, DJ1, PINK1, and LRRK2. The first three genes were found in affected individuals who had siblings with the condition but whose parents did not have Parkinson’s disease (recessive inheritance). There is some research to suggest that these genes may also be involved in early-onset PD (diagnosed before the age of 30) or in dominantly inherited PD but it is too early yet to be certain. The most recently discovered gene (LRRK2) has been reported in families with dominant inheritance. Changes in this gene may account for 5-10% of dominantly inherited Parkinson’s disease.
What determines who gets Parkinson’s disease?
In most cases inheriting a non-working copy of a single gene will not cause someone to develop Parkinson’s disease. We believe that many other complicating factors such as additional genes and environmental factors determine who will get the condition, when they get it and how it affects them. In the families we have studied, some people who inherit the gene develop the condition and others live their entire lives without showing any symptoms. There is a lot of research on genes and the environment that is attempting to understand how all these factors interact.
Genetic Testing in Parkinson’s Disease
Genetic testing has recently become available for the parkin and PINK1 genes. Parkin is a large gene and testing is difficult. At the current stage of understanding, testing is likely to give a meaningful result only for people who develop the condition before the age of 30 years. Pink1 appears to be a rare cause of inherited Parkinson’s disease. A small percentage (~2 percent) of those developing the condition at an early age appear to carry mutations in the PINK1 gene.
Current NHGRI Research on Parkinson’s Disease
NHGRI continues to study families in which three or more people are affected with Parkinson’s disease. If participants are willing, we share their samples (anonymously) with other researchers who are studying inherited Parkinson’s disease by submitting the samples to the NINDS DNA and Cell Line Parkinson’s Disease Repository [locus.umdnj.edu].
Genetic Analysis of Parkinson’s Disease: The purposes of this study are to identify the gene or genes responsible for an inherited form of Parkinson’s disease and learn more about how the disease develops.
PET Scanning in Parkinson’s Disease: NHGRI is also interested in detecting small changes in the brain and blood proteins. This study will compare brain blood flow and the brain’s use of dopamine in patients with Parkinson’s disease, their family members and normal volunteers.