Etiology Of Parkinson’s Disease
Thomas Gasser, … Mahlon R. DeLong, in, 2015
Etiology of Parkinson Disease: Clues from Epidemiology and Genetics285
Epidemiology and Environmental Risk Factors285
Genetic Causation of Parkinson Disease286
Autosomal Dominant Forms of Parkinson Disease286
Autosomal Recessive Forms of Parkinson Disease287
Genetic Risk Factors for Sporadic Parkinson Disease288
Genetic Models for Parkinson Disease288
Selective Neuronal Degeneration in Parkinson Disease289
Pathology and Pathogenesis289
Relationship between Parkinson Disease and Multiple Systems Atrophy290
Pattern of Dopamine Loss in the Striatum293
Discharge Rate Changes in the Basal Ganglia293
Changes in Activity Patterns of Basal Ganglia Networks294
Relationship of Rate and Pattern Changes to Parkinsonism294
Role of Non-Motor Basal Ganglia Circuits in Parkinson Disease295
Roger C. Duvoisin, in, 1981
What Can You Do If You Have Pd
- Work with your doctor to create a plan to stay healthy. This might include the following:
- A referral to a neurologist, a doctor who specializes in the brain
- Care from an occupational therapist, physical therapist or speech therapist
- Meeting with a medical social worker to talk about how Parkinson’s will affect your life
For more information, visit our Treatment page.
Page reviewed by Dr. Chauncey Spears, Movement Disorders Fellow at the University of Florida, a Parkinsons Foundation Center of Excellence.
Who Gets Parkinson’s Disease
Approximately one million Americans have Parkinson’s disease, including three out of every 100 people over the age of 60. Over 50,000 Americans are diagnosed with Parkinson’s disease each year. There is increasing evidence that Parkinson’s disease may be inherited . Men are slightly more likely to develop the disease than women.
The average age at which it is diagnosed is 60. However, about 4% of those with Parkinson’s disease are diagnosed before age 50, and about half of those are diagnosed before age 40. When the diagnosis is made early, it is referred to as “young-onset” Parkinson’s disease.
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Genetics Of Parkinsons Disease
A detailed review of the genetics of PD is beyond the scope of this chapter, and readers are referred to recent reviews.103,104 In brief, a refined knowledge of the genetic factors involved in familial PD has led to better understanding of pathological cellular processes that may be common to all forms of the disease, including mitochondrial dysfunction, oxidative stress, and abnormal protein processing.
The most commonly inherited form of PD is caused by an autosomal dominant mutation in the leucine-rich repeat kinase 2 protein, a kinase whose substrates have been elusive.105107 Mutant LRRK2 has been associated with dysregulation of macroautophagy as well as mitochondrial abnormalities.108,109 LRRK2 mutations display variable, age-dependent penetrance and have also been found in idiopathic PD, suggesting that other risk factors for the disease affect the risk associated with LRRK2 mutations.110 The degree to which LRRK2 contributes to idiopathic disease is uncertain, but there is hope that LRRK2 kinase inhibitors may be beneficial for at least some forms of PD.
In summary, a large number of genetic mutations have been associated with PD. In general, these genes fall into categories affecting mitochondria, proteostasis/autophagy, and oxidative stress. The role of these proteins in idiopathic PD is an area of active investigation and appears to be leading to new therapeutic strategies.
Theories About What Causes Parkinsons
The cause of Parkinsons disease is still unknown, although there is some evidence for the role of genetics, environmental factors, or a combination of both. It is also possible that there may be more than one cause of the disease. Scientists generally believe that both genetics and environment interact to cause Parkinsons disease in most people who have it.
Currently, there is an enormous amount of research directed at producing more answers about what causes Parkinsons disease and how it might be prevented or cured. When physicians diagnose Parkinsons, they often describe it as idiopathic . This simply means that the cause of the disease is not known.
Is Parkinsons Disease Inherited
Scientists have discovered gene mutations that are associated with Parkinsons disease.
There is some belief that some cases of early-onset Parkinsons disease disease starting before age 50 may be inherited. Scientists identified a gene mutation in people with Parkinsons disease whose brains contain Lewy bodies, which are clumps of the protein alpha-synuclein. Scientists are trying to understand the function of this protein and its relationship to genetic mutations that are sometimes seen in Parkinsons disease and in people with a type of dementia called Lewy body dementia.
Several other gene mutations have been found to play a role in Parkinsons disease. Mutations in these genes cause abnormal cell functioning, which affects the nerve cells ability to release dopamine and causes nerve cell death. Researchers are still trying to discover what causes these genes to mutate in order to understand how gene mutations influence the development of Parkinsons disease.
Scientists think that about 10% to 15% of persons with Parkinsons disease may have a genetic mutation that predisposes them to development of the disease. There are also environmental factors involved that are not fully understood.
In The Loop: Staying Ahead Of Parkinsons Disease One Ping Pong Game At A Time
Since being diagnosed with Parkinson’s disease, Steve Grinnell has worked hard to stay active, stepping up his table tennis game and, thanks to co-workers, testing his skills outside his home.
Four years ago, Steve Grinnell’s life was forever changed when doctors at Mayo Clinic in Rochester diagnosed him with early-onset Parkinson’s disease. Since that time, the progressive nervous system disorder has begun to take a toll on Steve and his family, just as it does on the millions of other Americans living with the disease. “It has greatly diminished his quality of life, leaving him with tremors, physical exhaustion, impaired balance, troubled grasping things with his right hand, slow right-arm movement and problems sleeping,” the Rochester Post-Bulletin recently reported. “That’s to name just a few of his symptoms.”
Reading that, one might assume the disorder is winning. And to Steve, sometimes it feels like it is. But much of the time, he tells us he also feels like he’s staying one step ahead of the disease by staying as physically active as possible. “Parkinson’s presents such a conundrum because it wears you down physically, and yet exercise is so valuable,” Steve says. “My legs, feet and right arm are always cramping, so it takes mental effort to get moving.”
What Is The Outlook For Persons With Parkinsons Disease
Although there is no cure or absolute evidence of ways to prevent Parkinsons disease, scientists are working hard to learn more about the disease and find innovative ways to better manage it, prevent it from progressing and ultimately curing it.
Currently, you and your healthcare teams efforts are focused on medical management of your symptoms along with general health and lifestyle improvement recommendations . By identifying individual symptoms and adjusting the course of action based on changes in symptoms, most people with Parkinsons disease can live fulfilling lives.
The future is hopeful. Some of the research underway includes:
- Using stem cells to produce new neurons, which would produce dopamine.
- Producing a dopamine-producing enzyme that is delivered to a gene in the brain that controls movement.
- Using a naturally occurring human protein glial cell-line derived neurotrophic factor, GDNF to protect dopamine-releasing nerve cells.
Many other investigations are underway too. Much has been learned, much progress has been made and additional discoveries are likely to come.
Neuropathology Of Parkinsons Disease
Macroscopically, the brain in idiopathic PD is often unremarkable with mild atrophy of the frontal cortex and ventricular dilation in some cases. The main distinctive morphological change in the PD brain is observed in transverse sections of the brainstem, where almost all cases present with loss of the darkly pigmented area in the substantia nigra pars compacta and locus coeruleus. This pigmentation loss directly correlates with the death of dopaminergic neuromelanin-containing neurons in the SNpc and noradrenergic neurons in the locus coeruleus . Cell death in the SNpc is mostly restricted to a specific group of neuromelanin-containing dopaminergic neurons, namely the A9 neurons, while other neuronal and glial cell types are largely spared .
Coronal section at the level of the substantia nigra pars compacta in a control and a PD brain stained by hematoxylin and eosin. In both sections, the dark brown cells are the neuromelanin-containing dopaminergic neurons.
Dietary Factors In The Etiology Of Parkinsons Disease
Jason R. Cannon
1School of Health Sciences, Purdue University, 550 Stadium Mall Dr., West Lafayette, IN 47907, USA
Parkinsons disease is the second most common neurodegenerative disorder. The majority of cases do not arise from purely genetic factors, implicating an important role of environmental factors in disease pathogenesis. Well-established environmental toxins important in PD include pesticides, herbicides, and heavy metals. However, many toxicants linked to PD and used in animal models are rarely encountered. In this context, other factors such as dietary components may represent daily exposures and have gained attention as disease modifiers. Several in vitro, in vivo, and human epidemiological studies have found a variety of dietary factors that modify PD risk. Here, we critically review findings on association between dietary factors, including vitamins, flavonoids, calorie intake, caffeine, alcohol, and metals consumed via food and fatty acids and PD. We have also discussed key data on heterocyclic amines that are produced in high-temperature cooked meat, which is a new emerging field in the assessment of dietary factors in neurological diseases. While more research is clearly needed, significant evidence exists that specific dietary factors can modify PD risk.
2.1. Vitamin A and Carotenoid
2.2. Vitamin B
2.3. Vitamin C
2.4. Vitamin D
2.5. Vitamin E
4. Calorie Intake
Trouble Moving Or Walking
Do you feel stiff in your body, arms or legs? Have others noticed that your arms dont swing like they used to when you walk? Sometimes stiffness goes away as you move. If it does not, it can be a sign of Parkinson’s disease. An early sign might be stiffness or pain in your shoulder or hips. People sometimes say their feet seem stuck to the floor.
What is normal?If you have injured your arm or shoulder, you may not be able to use it as well until it is healed, or another illness like arthritis might cause the same symptom.
The Genetics Of Parkinsons
A 2020 study including 1,676 people with Parkinsons in mainland China suggested that genes play a role in the development of the condition. An estimated 10 to 15 percent of people with Parkinsons have a family history of the condition.
In fact, a number of specific genes have been linked to the development of Parkinsons.
How do genetics factor into Parkinsons in some families? According to Genetics Home Reference, one possible way is through the mutation of genes responsible for producing dopamine and certain proteins essential for brain function.
Lewy Bodies And Alpha
In addition to the dopamine deficiency and neuronal loss, PD is also associated with a buildup of intracellular inclusions inside the neurons, called Lewy bodies. Studies have shown that the Lewy bodies are made mainly of a protein called alpha-synuclein.
They are not seen in brain imaging studies but have been detected in research studies that examine the brains of people who had PD and donated their own brains to science for the purpose of research. There is no known treatment or method of removing the Lewy bodies at this time.
In PD, Lewy bodies are found in the substantia nigra as well as other areas, including the amygdala and locus coeruleus , the raphe nucleus , and the olfactory nerve . The functions controlled by these regions can be impaired in PD, although the symptoms arent as noticeable as the tremors and muscle stiffness.
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What Role Do Genes Play
Your genes are like your body’s instruction book. So if you get a change in one of them, it can make your body work in a slightly different way. Sometimes, that means you’re more likely to get a certain disease.
There are several genetic mutations that can raise your risk for Parkinson’s, each by a little bit. They have a part in about 1 in 10 cases.
If you have one or more of these changes, it doesn’t mean you’ll get Parkinson’s. Some people will, but many won’t, and doctors don’t know why. It may have to do with other genes or something in your environment.
Lack Of Exercise/physical Activities
The idea that exercise might have a role in Parkinsons disease is not new. Researchers have been trying to find a connection between Parkinsons and exercise for many years. They think that those who do regular exercise are less likely affected by the disease than those who dont.
A study published in the Journal of Neurology suggests that higher levels of physical activity may reduce the risk of developing Parkinsons disease. In this study, 125,828 provided information on physical activity in early adulthood. During the follow-up, a total of 387 Parkinsons cases were identified. The study found that the people who didnt develop the disease were mostly involved in some sort of higher levels of physical activity.
Similarly, one meta-analysis that included data from 8 prospective studies has concluded that moderate to vigorous physical activity may have an inverse relationship with a risk of Parkinsons.
Although it is not known how exercise could protect someone from developing Parkinsons, researchers think that it may inhibit abnormal changes in dopamine neurons and contribute to the healthy functioning of brain parts involved in body movement.
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Interaction Between Genes And Environmental Insults
-Synuclein monomers are known to aggregate into protofibrillary oligomers and later into fibrils and Lewy bodies. This process of fibrilization is accelerated by nucleation, iron and copper , the A53T mutation , and the presence of ROS. It is possible that toxins such as MPTP impair mitochondrial function and thus lead to an increase in the concentration of radicals in the neurons, especially if they metabolize dopamine. In the highly oxidative environment found in dopaminergic neurons, the elevated levels of ROS lead to further -synuclein oligomerization, which causes the demise of the dopamine neurons via the toxic oligomeric species. The oligomers are thought to further lead to generation of more ROS, thus creating a vicious cycle of death for the dopaminergic neurons of the substantia nigra pars compacta . This may be one link between the genetic and environmental causes of PD.
Symptoms Of Parkinson’s Disease
These common symptoms of Parkinson’s disease often begin gradually and progress over time:
- Shaking or tremor
- Poor posture
- Slowing of body movements
As the disease continues to progress, additional symptoms can occur such as slurred or soft speech, trouble chewing and/or swallowing, memory loss, constipation, trouble sleeping, loss of bladder control, anxiety, depression, inability to regulate body temperature, sexual dysfunction, decreased ability to smell, restless legs and muscle cramps.
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What Are Lewy Bodies
Alpha-Synuclein is a protein found exclusively in neurons. In PD, a-Synuclein is found in globs known as Lewy bodies that are found in neurons.
Lewy bodies are found in dopaminergic neurons in the substantia nigra pars compacta and likely contribute to the death of these neurons. Lewy bodies can be found in other brain areas such as the amygdala, locus coeruleus, and raphe nucleus.
These brain areas play a role in anxiety and depression. A brain area called the cortex is responsible for cognition, and executive function, i.e. the ability to plan for the future. Lewy bodies in this area of the brain are thought to cause dementia.
The Five Environmental Causes Of Parkinsons Disease
Parkinsons disease is a brain disorder that develops and becomes worse over time. The typical symptoms of the disease include tremor, stiffness, slowness of movement, and balance problems. These symptoms develop when the brain lost its ability to produce a sufficient amount of dopamine, a neurotransmitter responsible for controlled body movement.
Researchers have identified a variety of environmental factors that are linked to Parkinsons disease. Some of these factors may directly cause the disease symptoms, others may increase the risk of developing it.
Here are the 5 main environmental factors that are linked to Parkinsons disease development.
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What Are The Symptoms Of Parkinson’s Disease
The main symptoms of Parkinson’s disease are:
- tremor or shaking, often when resting or tired. It usually begins in one arm or hand
- muscle rigidity or stiffness, which can limit movement and may be painful
- slowing of movement, which may lead to periods of freezing and small shuffling steps
- stooped posture and balance problems
The symptoms of Parkinson’s disease vary from person to person as well as over time. Some people also experience:
- loss of unconscious movements, such as blinking and smiling
- difficulties with handwriting
- drop in blood pressure leading to dizziness
- difficulty swallowing
Many of the symptoms of Parkinson’s disease could be caused by other conditions. For example, stooped posture could be caused by osteoporosis. But if you are worried by your symptoms, it is a good idea to see your doctor.