Etiology of Parkinson Disease

Although the etiology of Parkinson disease (PD) is unknown, it is believed to be multifactorial and is likely to involve a complex interaction of environmental and genetic factors (Fig. 2.1).

Traditionally, environmental factors, especially exposure to pesticides and herbicides, have demonstrated a strong association with the onset of PD, due to its dopaminergic neuron toxicity.²⁶ Rural residency, farming, and consumption of well water appears to increase the risk of PD and may provide further evidence in support of herbicides or pesticide as critical etiological factors.²⁶

Several other environmental factors may also be considered as risk contributors of PD. Specifically, a history of head injury has been observed with PD in later life. Non-smokers and non-caffeinated beverage drinkers are believed at higher risk. Further, low blood uric acid levels tend to be associated with increased risk of PD. The mechanisms by which these contribute to PD remain unknown.²⁷

Recent research has been focused on the genetic factors involved. Around 15% of individuals with PD have a first-degree relative also suffering from the same condition.²⁷ Several studies of familial PD show inheritance patterns of both autosomal dominant and recessive.^{26 ,​ 27} Several twin studies suggest an increased concordance rate of early onset PD in monozygotic twins.^{26 ,​ 27 ,​ 28}

Genetic mutations implicated in the development of PD are often involved in protein handling, oxidative stress, and mitochondrial function, including LRRK2, SNCA, PINK1, PARK7, GBA, DJ1, PARK2.²⁹ Again, one or several mutations in these genes alone does not determine the onset. A combination of these genetic mutations with environmental factors could affect age of onset, severity, and progression in a way that has yet to be defined.