Brain Primer

Making Sense of Parkinson’s Disease

  • Reviewed10 Apr 2023
  • Author Clinton Parks
  • Source BrainFacts/SfN
Nurse holding older man's hand via Inside Creative House

Parkinson’s disease is the second most common neurodegenerative disorder in humans. Like Alzheimer’s disease, its incidence increases with age, with the average onset around age 60. About 5 million people in the world’s 10 most populous countries have Parkinson’s, and its frequency is expected to double by 2030. With 50,000 to 60,000 cases diagnosed annually in the U.S., the actual figures may be much higher — especially since early symptoms can be mistaken for normal aging and thus are not reported.

From 2000 to 2013, the age-adjusted death rates for those with Parkinson’s disease increased in the U.S. from 8.8 to 11.0 per 100,000 for males and from 3.9 to 4.8 per 100,000 for females. For reasons not yet fully understood, the disease is more prevalent in males than in females. About 5% to 10% of cases are “early-onset,” occurring before age 50. Rarer still, patients with “juvenile Parkinsonism” may develop symptoms before age 20.

Estimates of the prevalence, or overall number, of Parkinson’s patients vary widely, so incidence — the occurrence of new cases within a given time period (for example, per year) — is a better index for this disease. There is a higher incidence of Parkinson’s in developed countries, but the reason is unknown. Although, increased risk of the disease has also been reported in areas with increased pesticide use.


At first, Parkinson’s is characterized by motor problems: slow movement; muscular rigidity; poor coordination and instability; and shaking in hands, arms, legs, jaw, and face while at rest. As the disease progresses, the shaking, known as resting tremor, may worsen and interfere with walking, talking, and other simple tasks. Cognitive decline often presents at later stages. Some people develop depression and other emotional changes, difficulty swallowing and chewing, skin problems, constipation, or urinary problems, and sleeping problems. However, the rate and intensity of Parkinson’s progression vary. Some people become severely disabled, while others have only minor motor disruptions.

Pathology and Causes

Parkinson’s is a motor system disorder caused by the loss of dopamine-producing cells neurons in the substantia nigra — a midbrain structure that is considered part of the basal ganglia. This brain region affects movement, reward, and addiction. At the cellular level, the death of neurons likely arises as a result of damage to mitochondrial respiration.

Some early-onset cases are linked to mutations in the PARK2 (or PRKN) gene, which codes for the protein “parkin.” Most types of Parkinson’s are caused by a combination of genetics and environment, but an estimated 15% to 25% of people with adult-onset Parkinson’s have a known relative with the disease. Genes like alpha-synuclein (SNCA), repeat kinase 2 (LRRK-2), and glucocerebrosidase (GBA) also point to the importance of genetics as a causal factor. 

While Parkinson’s and Lewy body dementia are sometimes considered different disorders, Lewy bodies, accumulations of proteins in neuron bodies, have been implicated in both diseases. Lewy bodies are mainly composed of the protein alpha-synuclein entangled with other proteins, including neurofilament, ubiquitin, alpha B crystallin, and probably tau protein in neurofibrillary tangles. The Lewy body protein, alpha-synuclein, is involved in dopamine transport in the nervous system. 

There is no definitive test for Parkinson’s. So without accepted biomarkers, diagnosis is based on medical history and neurological tests that can include brain scans. Accurate diagnosis can be difficult, because some non-Parkinson’s conditions display similar symptoms. In the future, mitochondrial molecules could be a potential source of a Parkinson’s biomarker. 


Scientists can treat mice with the chemical MPTP (1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine) to create an animal model that can provide further insight into Parkinson’s. In the body, MPTP metabolizes into the neurotoxin MPP+ (1-methyl-4-phen- ylpyridinium), which causes a Parkinson’s-like loss of cells in the substantia nigra and cognitive deficits. However, MPTP does not perfectly mimic the symptoms of human Parkinson’s disease, including the motor deficits. 

Research on using stem cells to replace damaged dopamine neurons in Parkinson’s patients has shown promise. There are two types of stem cells: the more flexible (and controversial) fetal tissue and induced pluripotent stem (iPS) cells, which are specialized adult (often blood or skin) cells that have been repurposed into a generalized embryonic state. There have been successful lab studies using iPS cells, and positive to mixed results in clinical studies with the fetal stem cells. A 2017 Kyoto University study transferred human iPS cells into the brains of monkeys treated with MPTP. Two years after this transplantation, the treated monkeys were shown to have healthy DA neuron integration, growth, and even functioning in the striatum. 


Treatment with levodopa (L-Dopa) temporarily relieves Parkinson’s motor symptoms but does not slow disease progression. The long-term use of L-Dopa can induce dyskinesia — abnormal and uncontrolled involuntary movements. Strategies for treating Parkinson’s include gene therapy and targeting specific cellular molecules. 

A surgical procedure called deep brain stimulation (DBS) is increasingly used to treat Parkinson’s patients whose symptoms, including rigidity, tremor, slowed movement, and mobility problems, do not respond adequately to medication. The DBS technique implants a small neurostimulator device — like a pacemaker — that sends electrical impulses that interfere with and block brain signals that cause the motor symptoms of Parkinson’s. Before implanting a neurostimulator into the brain, the neurosurgeon locates where the patient’s symptoms are originating from, using MRI or CT scans. Most often, the problem areas in the brain are the thalamus, the subthalamic nucleus, and a portion of the globus pallidus (part of the basal ganglia). After the imaging, microelectrode recording — which involves a small wire that monitors the activity of nerve cells in the target area — is sometimes used to further localize problem areas in the brain. This approach has proven to be highly successful with a segment of patients.

One treatment still in the research stage is a strategy to break apart Lewy bodies. The idea is to use high hydrostatic pressure to break apart aggregated alpha-synuclein fibril plaques, like those found in Lewy bodies, and return the protein to its properly functioning form. Researchers are exploring Parkinson’s disease prevention through epidemiological studies. Some scientists have found that the disease is less common among coffee drinkers and cigarette smokers. If caffeine and nicotine offer protection, this could reflect some central action that benefits the brain’s dopaminergic systems. 

Adapted from the 8th edition of Brain Facts by Clinton Parks.



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