Etiology and Pathophysiology

The primary cause of PD is still unknown, and genetic and environmental risk factors have been associated with the disease. Most symptoms are due to loss of dopaminergic neurons; however, other neurotransmitters have been associated with Parkinson’s.


Here are the highlights of etiology and pathophysiology.


Primary cause of PD is unknown. Genetic and environmental factors have been associated with PD.  Recent findings< suggest that Parkinson's disease can be transmitted via a prion-like mechanism and is associated with mis-folded aplha-synuclein<

Risk Factors

  • Age
  • Family history
  • Exposure to well water
  • Rural living–possible link to exposure to pesticides
  • Certain professions, such as healthcare workers, farmers, teachers
  • Male sex


  • Eleven genes have been associated with PD.
  • Genetic forms account for about 10% to 15% of PD.
  • Having a first degree relative with PD increases your chances of getting PD perhaps 2- or 3-fold, which is perhaps a 3% lifetime risk (compared to 1%-1.5% for the general population).
  • Genetic testing< is predominantly done in academic centers with very few commercially available tests.


The symptoms and signs of PD are predominantly due to loss of dopaminergic neurons in the substantia nigra of the midbrain. Most symptoms will appear after 60% to 80% of the cells become impaired or die. The results of cell death cause abnormal activity in the basal ganglia, which usually causes the motor symptoms of the disease.

The pathological hallmark of PD is the Lewy bodyi, made predominantly of alpha-synuclein and other ubiquitinated damaged proteins.

Significant cholinergic and serotoninergic deficits may account for some non-motor symptoms (cognitive impairment/dementia and depression) that are common in PD as it progresses. 

Parkinson's disease has been associated with

  • Increased oxidative stress
  • Mitochondrial dysfunction
  • Protein aggregation (alpha-synuclein)
  • Proteasomal dysfunction
See Also: Genetic Testing

Pahwa R, Lyons KE, eds. Handbook of Parkinson’s Disease. 4th ed. New York, NY: Informa Healthcare; 2007.