Other Causes Of Parkinsonism
Parkinsonism is the umbrella term used to describe the symptoms of tremors, muscle rigidity and slowness of movement.
Parkinsons disease is the most common type of parkinsonism, but there are also some rarer types where a specific cause can be identified.
These include parkinsonism caused by:
- medication where symptoms develop after taking certain medications, such as some types of antipsychotic medication, and usually improve once the medication is stopped
- other progressive brain conditions such as progressive supranuclear palsy, multiple systems atrophy and corticobasal degeneration
- cerebrovascular disease where a series of small strokes cause several parts of the brain to die
You can read more about parkinsonism on the Parkinsons UK website.
Page last reviewed: 30 April 2019 Next review due: 30 April 2022
What Should You Know About At
Genetic tests are not a substitute for a Parkinson’s diagnosis. Most at-home genetic tests do not provide genetic counseling services to help interpret the results. Always consult with a genetic counselor and your doctor before and after taking a genetic test. Most at-home genetic tests check for a limited number of gene mutations associated with Parkinson’s. This can be misleading since these tests may not be comprehensive.
Since scientists are still discovering more PD-associated genes, it is important to consult your doctor about comprehensive genetic testing options, like the PD GENEration study, which provides a free comprehensive genetic test identifying all possible variants in the two most common PD genes.
Even if you or a loved-one test positive for a Parkinson’s gene, it does not mean either of you will develop it. Having a genetic mutation only means that you may be at increased risk to develop PD. Environmental factors and lifestyle choices will help determine whether someone will get Parkinson’s.
How Does Environment Come Into It
Your environment is a hard one to pin down. Partly, thats because it covers a lot of ground. Its everything thats not your genes, which could mean where you live, what you eat, chemicals youve come into contact with, and more.
Not only that, but it could take years for the effects from something in your environment to show up. So far, doctors have a lot of clues but no smoking gun. So you could have people who live or work in an area around chemicals tied to Parkinsons, but many of them dont get it.
Some research shows links between Parkinsons and:
- Agent Orange, a chemical used to destroy trees and crops in the Vietnam War.
- Certain chemicals used in farming, such as insecticides, herbicides, and fungicides.
- Some metals and chemicals used in factories, such as manganese, lead, and trichlorethylene .
These can come into play based on where you live, what you do for work, or if you served in the military. Sometimes, these chemicals seep into well water, so thats one more way they can affect you.
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Genetic Susceptibility Factors In Parkinson’s Disease
Monogenic forms represent less than 10% of PD in most populations. The vast majority result from complex interactions among genes and between genes and environmental factors. Genetic variations may be susceptibility factors or disease modifiers, affecting penetrance, age at onset, severity and progression. High-density arrays of single nucleotide polymorphisms permit the identification of susceptibility factors in genome-wide association studies, in which the frequencies of putative risk alleles are compared in patients and controls.
Genetic Factors In Parkinsons Disease
For many years, it was thought that most forms of Parkinsons disease did not have a genetic basis. But by the late 1990s, studies in a number of patient populations documented that the risk of Parkinsons disease among first-degree relatives of an affected individual is 2 to 14 times higher than the risk in the general population. As genome technologies have become more cost-effective and precise, genetic linkage maps have improved dramatically, allowing more research into the genetic cause of disease. Entire genome sequence analyses are now being completed on individual patients at a reasonable and ever-dropping price.
There are a small number of genes that are known to be involved in up to 6% of total PD cases, and there are probably other genes that increase the potential risk of Parkinsons, without necessarily causing it. Up to 15% of PD patients have a direct family member who has also had PD.
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Studies Of Pd With Patient
The discovery of iPSC technology,, has offered the capacity to generate live brain tissue from healthy subjects and patients for studying neurodegenerative diseases. Directed reprogramming and neuronal differentiation of iPSCs allows the study of specific neuronal subtypes. Human-derived neurons offer a unique opportunity for modeling real cases of human genetic diseases in vitro. The ability to generate neurons both from PD patients and healthy control individuals allows the identification of early disease-linked phenotypes and provides a new paradigm for preclinical drug development and validation .
Fig. 3: Using brain cells generated from patient-derived iPSC to study PD in vitro.
What Are The Benefits Of Genetic Testing
ESCAPE is developing a new therapy for patients with Parkinson’s disease caused by a mutation in theLRRK2 gene. It is hoped that this therapy may be able to stop or slow the progression of the disease. Since most people with Parkinsonâs disease have never been tested for LRRK2 mutations, ESCAPE is providing free genetic testing via mail which is an at-home saliva test. If a patient is found to have a mutation in theLRRK2 gene they will be invited to take part in certain clinical studies for patients with Parkinson’s disease and this specific gene mutation.
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Genes Connected To Parkinson’s
In 1997, researchers at the National Institutes of Health made the first Parkinsons genetic connection, discovering that mutations in the SNCA gene were common in several families who had many members with Parkinsons. While mutations in this gene are rare, they have taught us invaluable information about PD.
The SNCA gene instructs the body to make the protein alpha-synuclein, which for reasons that are not yet known, clumps in the brain cells of people with PD. Study of the SNCA gene led to this understanding that applies to nearly all people with the disease. Since then, alpha-synuclein has been a major target of new drugs for Parkinsons.
Another gene that plays a role in Parkinsons is LRRK2, which accounts for one to two percent of all cases. For people of particular ethnic backgrounds Ashkenazi Jewish and North African Berber descent mutations in the LRRK2 gene account for a much greater number of cases than in the general PD population. Mutations in LRRK2 lead to too much activity of the LRRK2 protein, though recent research indicates people without a mutation can also have overactivity of LRRK2.
Shake It Up are funding several studies into LRRK2 and you can learn more about these here.GBA
Genetics: Insights Into Etiology
Improvement in genetic analysis techniques in the 1990s led to the discovery of the first genetic cause of PD: mutations in the SNCA gene encoding -synuclein . At around the same time, -synuclein was found to be the major constituent of LB, the pathological hallmark of PD . Subsequently, multiplications of the SNCA gene have been found to cause PD with penetrance increasing with gene dosage . These discoveries brought -synuclein to center stage in the study of the pathogenesis of PD and led to the hypothesis that during different stages of the disease, -synuclein spreads in a stereotypical way within the nervous system in a prion-like fashion .
Table 2 Examples of genes associated with PD risk
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What Is The Number 1 Cause Of Parkinson’s
“Scientists believe the disease is caused by an interaction of genes, environmental and lifestyle influences, so we are not able to narrow it down to one top cause,” says Beck. “One thing that all people with PD have in common is they have lost and continue to lose dopaminergic neurons in their brain. We are currently trying to understand why that happens and how we stop it.” Keep reading to learn about how your genetics may play a role.
What Are The Complications Of Parkinson Disease
Parkinson disease causes physical symptoms at first. Problems with cognitive function, including forgetfulness and trouble with concentration, may arise later. As the disease gets worse with time, many people develop dementia. This can cause profound memory loss and makes it hard to maintain relationships.
Parkinson disease dementia can cause problems with:
- Speaking and communicating with others
- Problem solving
- Paying attention
If you have Parkinson disease and dementia, in time, you likely wont be able to live by yourself. Dementia affects your ability to care of yourself, even if you can still physically do daily tasks.
Experts dont understand how or why dementia often occurs with Parkinson disease. Its clear, though, that dementia and problems with cognitive function are linked to changes in the brain that cause problems with movement. As with Parkinson disease, dementia occurs when nerve cells degenerate, leading to chemical changes in the brain. Parkinson disease dementia may be treated with medicines also used to treat Alzheimers disease, another type of dementia.
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Concluding Remarks And Future
Genes implicated in Mendelian forms of PD have provided new insights into the pathogenesis of the disease. The molecular pathways identified in monogenic cases may also be implicated in sporadic PD. The effect of dosage of SNCA on the phenotype of patients with duplications or triplications is illustrative. In addition, non-coding variants in this gene, thought to affect the level of expression in neurons, are associated with risk of the disease. The molecular mechanisms that contribute to PD and related disorders result in the death of dopaminergic neurons in vulnerable brain regions, and consequently the shared phenotype. However, known PD-causing genes account for only a small fraction of monogenic forms. Robust high-density SNP genotyping technologies and data analysis programs, combined with the analysis of copy number variations and large pathogenic genomic rearrangements, will identify novel loci. The clinical heterogeneity of parkinsonism is probably the cumulative effect of different gene-environment and/or genegene interactions. To identify risk variants in PD, association study methodology must be improved. Studies in isolated and heterogeneous populations, and approaches that minimize population stratification, are needed. Large-scale studies and publicly available GWA databases, crucial for statistical power, require collaborative efforts with shared sets of stringent clinical, genetic and analytic methods.
Why Is It So Important To Know This Information
“If you have PD, it is important to know if you have a genetic component,” says Beck. “The next generation of PD treatments will likely target specific, genetic forms of PD an approach we have seen in some cancer treatments. By equipping yourself with knowledge about the genetics of your disease, you may be eligible for clinical trials that are testing new/experimental treatments specific to your genetic makeup.”
- Trembling of hands, arms, legs, jaw and face
- Stiffness of the arms, legs and trunk
- Slowness of movement
- Poor balance and coordination
The Parkinson’s Foundation offers people with PD genetic testing and counseling at no cost through its ongoing research study, PD GENEration: Mapping the Future of Parkinson’s Disease, says Beck. The Parkinson’s Foundation also has resources available at Parkinson.org, or you can call the Parkinson Foundation Helpline at 1-800-4PD-INFO . And to get through this pandemic at your healthiest, don’t miss these 35 Places You’re Most Likely to Catch COVID.
Eat This, Not That!
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Reasons Why Parkinsons Disease Occurs
The scientific reason given for Parkinsons disease is that the patient has lost nerve cells in the part of the brain called the substantia nigra. A very important chemical called dopamine is produced by the substantia nigra. The loss of the ability to produce dopamine contributes to the early stages of Parkinsons disease.
Faqs: Genetics & Parkinsons
If I have Parkinson’s disease will my child get it too? Will I inherit Parkinson’s if my parent or grandparent has it?
Most people with Parkinson’s have no known genetic link. Their children will likely never develop Parkinson’s. There are some known genetic variations that increase the risk of getting Parkinson’s, but most people with these variations do not get Parkinson’s. Like many other diseases, Parkinson’s is a result of a complex interaction between genes and environmental factors.
In a small number of people , Parkinson’s is inherited and can affect multiple family members. Their children may have a higher risk of developing Parkinson’s. However, there is no guarantee they will develop PD.
What if my genetic test is positive for a Parkinson’s gene?
Scientists have identified several genetic mutations that can increase the risk of developing Parkinson’s. If someone tests positive for a mutation in a Parkinson’s gene, it does not necessarily mean they will develop PD. Some people who have mutations in the genes associated with Parkinson’s never develop PD. A person may inherit a hereditary genetic mutation that increases their risk for Parkinson’s; however, they may also inherit other genes, be exposed to environmental factors or have lifestyle choices that offset the risk. Genetic testing is currently available for the following genes related to Parkinson’s: GBA, PARK7, SNCA, LRRK2, parkin and PINK1.
What can I do with my genetic test results?
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When To See A Doctor About Parkinsons
There isnt one specific test to diagnose Parkinsons disease. Doctors will usually evaluate your symptoms and perform several tests to determine if you have the condition. If you notice the following early warning signs, then you should see a doctor.
The early warning signs of Parkinsons disease include:
What If I Carry The Gene
There are ongoing clinical trials testing therapies to treat people who have Parkinson’s and carry certain gene mutations. Proving that it can be important to know which gene mutation you carry. Consult with your doctor when considering a genetic test to determine if you are eligible to participate in gene-based clinical trials.
The Parkinsons Foundation study,;PD GENEration: Mapping the Future of Parkinsons Disease, is the first national study to offer genetic testing and counseling at no cost for those with a confirmed Parkinsons diagnosis. Learn more and enroll at Parkinson.org/PDGENEration.
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Parkinsons Disease Diet And Nutrition
Maintaining Your Weight With Parkinsons Disease
Malnutrition and weight maintenance is often an issue for people with Parkinsons disease. Here are some tips to help you maintain a healthy weight.
- Weigh yourself once or twice a week, unless your doctor recommends weighing yourself often. If you are taking diuretics or steroids, such as prednisone, you should weigh yourself daily.
- If you have an unexplained weight gain or loss , contact your doctor. He or she may want to modify your food or fluid intake to help manage your condition.
- Avoid low-fat or low-calorie products. . Use whole milk, whole milk cheese, and yogurt.
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Are Genes Responsible For Monogenic Disorders Also Susceptibility Factors
Associations detected by screening candidate genes in controls and patients cannot always be replicated in follow-up studies, and few candidate genes were confirmed in meta-analysis, because of potential biases and confounding factors, including population stratification, small sample size, misclassification and/or inappropriate statistical methods. Polymorphic variants in SNCA and LRRK2 genes, and heterozygous mutations in the GBA gene, however, have been validated as genetic susceptibility factors .
Nucleotide polymorphisms located close to the promoter region and throughout SNCA have been associated with sporadic PD, although much of the data is equivocal . Rep1 , a mixed nucleotide repeat, 10 kb upstream of the translational start of SNCA , has been confirmed as a risk factor , and synergy between an SNCA variant and a polymorphism in microtubule-associated protein tau , each of which increases the risk for the development of PD, has been detected . The combination of risk genotypes in SNCA and MAPT doubles the risk of PD, further supporting the notion that the related pathways contribute to neurodegenerative diseases . The risk associated with Rep1 does not interact, however, with herbicide exposure, an independent risk factor in PD .
International Team Work To Study Genetic Forms Of Parkinsons Disease
In a scientific article published in 2019, a group of researchers present how an international collaboration involving many scientists can help to gather vast amount of data on a disease. While one researcher can lack clinical information on symptoms associated with specific forms of the disease, developing a global-scale collaborative database should help fill these knowledge gaps. In this case, the authors focused on monogenic forms of Parkinsons caused by a mutation on a single gene and, in a few weeks, made an inventory of the data available worldwide for over 8000 cases, demonstrating the potential of this approach.
How Environmental Factors And Aging Can Be Recapitulated In Vitro
An obvious limitation of in vitro models is the lack of environmental context. The influence of nongenetic factors is not recapitulated in the basal phenotype of patient-derived neurons. For example, the influence of head trauma of a boxer with sporadic PD will not be recapitulated by default in reprogrammed neurons. An alternative would be to transplant the patient-derived neurons in animals and simulate the trauma on the animal. Similarly, influence of decades of aging of the human brain is difficult to reproduce in vitro in a few months within the boundaries of feasible experimental design. Brains in a dish will always be an imperfect experimental model. However, many tricks can be used to recapitulate the environmental and aging stress in vitro. Table summarizes a list of reagents that have already been used in iPSC neuronal culture to mimic oxidative stress, proteostatic stress, mitochondrial stress, synaptic stress, ER stress, inflammation, and cellular aging. An interesting example is progerin, a truncated form of lamin A associated with premature aging. Increasing the expression of progerin in iPSC neurons can recapitulate at least some aspect of cellular aging in vitro. Human iPSC-derived dopamine neurons overexpressing progerin displayed specific phenotypes such as neuromelanin accumulation. In addition, PD patient-derived neurons revealed disease-related phenotypes that required both genetic susceptibility and induced-aging in vitro.