Do genetic factors protect against Parkinson's disease? What I can learn from my healthy grandma.

Parkinson's disease (PD) is a progressive, neurodegenerative disorder and it affects 4-5% of people age 85 years or older. The etiopathogenesis of PD is a consequence of interaction between two factors, environmental pathogens and genetic susceptibility. If an environmental agent such as a toxin or pathogen were to play a major role in the causality of PD, it would need to be something relatively ubiquitous in our environment since we cannot find a specific population at risk. On the other hand, all efforts to implicate specific genetic sequences in risk of PD were futile since the great majority of PD cases are sporadic; however, if the majority of the population is exposed to a culpable environmental factor and only 5% of the population 85 years or older manifest the disorder, this raises an important question: Why and how does vast majority of the population not manifest with PD? It seems that we should investigate the certain genome or epigenetic alterations of the unaffected 95%. This large non affected population might have PD but they are not yet symptomatic and some may not be so for at least another 10 or 20 years. To further address this issue, we should screen and study the population that have been exposed to the environmental factor but with high certainty are not yet affected. Therefore the perfect population would be non-PD subjects who are 90 years or older. We believe the following are the unmet research needs that deserve more attention in PD. (1) More genetic studies. Comparison should be between PD subjects and non-PD control subjects who are 90 years old and above. (2) Study the mechanism of action of the candidate genes, as a subsequent examination of their gene products may lead to the discovery of neuroprotective agents in the disease.