Causes and Risk Factors of Parkinson’s Disease

The cause of Parkinson’s disease remains largely unknown, but it is believed that a combination of genetics and environmental factors are at play. If a single cause of Parkinson’s disease can’t be identified, one or more risk factors may be to blame. Numerically speaking, genes account for about 10 to 15 percent of Parkinson’s disease, which is attributable to changes or mutations in genes inherited or passed down from one generation to the next. Certain ethnic groups are more likely to carry genes linked to Parkinson’s disease, namely Ashkenazi Jews and North African Arab Berbers, although researchers have not yet been able to determine why. As for the specific gene mutations, scientists have tied mutations in LRRK2, GBA, and SNCA genes to the development of Parkinson’s disease.

Genetics aside, environmental risk factors include head injury, area of residence, occupation, solvents and polychlorinated biphenyls, as well as exposure to pesticides, herbicides, and metals. Head injury refers to a traumatic brain injury that alters the level of consciousness, which seems to increase the risk of developing Parkinson’s disease some years later. As for area of residence and occupation, there are differences in both the geographic distribution of Parkinson’s disease and the incidence of Parkinson’s disease in certain occupational categories. Pesticide and herbicide exposure are linked to Parkinson’s disease, while metal exposure seems to be related to its development, but the exact connection is not entirely understood. Lastly, high concentrations of PCBs have been found in the brains of people with Parkinson’s disease.

No matter what the cause is, Parkinson’s disease arises from the death of dopaminergic neurons in the substantia nigra. This is part of the basal ganglia, a collection of brain regions that control movement through a connection with the motor cortex. The name substantia nigra means ‘black substance’ since it’s darker than other brain regions when looking at a slice of the brain on an autopsy. In Parkinson’s disease, these darker regions gradually disappear. Under a microscope, Lewy bodies are present in the affected substantia nigra neurons before they die, which are abnormal deposits of a protein called alpha-synuclein. The significance of Lewy bodies and the function of alpha-synuclein are both unknown, but scientists do know that they are found in other diseases as well.

Apart from potential genetic causes and environmental risk factors, other risk factors include age and gender. More specifically, the number of people diagnosed with Parkinson’s disease increases with age, regardless of sex, and approximately 1 percent of people over the age of 60 have the disease. As for gender, men are more likely to have Parkinson’s disease than women. In rare cases, Parkinsonian symptoms can be caused by MPTP. This is a toxic impurity that can be found in the recreational drug MPPP, or desmethylprodine, which is a synthetic opioid.

On the topic of causes and risk factors, scientists have identified a number of potential protective factors that may actually reduce the risk of developing Parkinson’s disease. These include the consumption of caffeine, higher uric acid or urate levels, regular intake of anti-inflammatory drugs, cigarette smoking, lower cholesterol levels, higher vitamin D levels, and increased physical activity.

Resources:
https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055
https://www.parkinson.org/Understanding-Parkinsons/Causes/Environmental-Factors
https://www.parkinson.org/understanding-parkinsons/causes/genetics