While waiting for Tup to get back from his trip, I've been doing a bit more thinking (always a dangerous thing!). Anyhow, here is the result.

Theory of PD
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To get PD, you must produce a lot of alpha-synuclein during your life, either by:
- having duplicates or triplicates of the SNCA gene (i.e. familial form of PD);
- having lots of viral/bacterial/fungal infections of the GI tract;
- growing old.

But not just normal alpha-synuclein. It must be alpha-synuclein which has one (or more) of the many possible mutations that cause it to mis-fold and aggregate, and prevent it from being cleared in the usual way.

Each mutation of alpha-synuclein only affects a small proportion of PwPs. But because there are many different mutations, they collectively affect a very large proportion of PwPs. [1]

[1] "... the common disease - common variant hypothesis, which states that genetic susceptibility to common diseases like hypertension, diabetes and PD are largely because of alleles that have moderate frequency in the population. ... While these known and yet unknown variants may individually contribute to a small proportion of disease susceptibility, collectively these variants could account for a significant fraction of disease risk." [A]

[A] Alpha-Synuclein and Familial Parkinson’s Disease, Pankratz et al., Mov Disord. 2009 June 15; 24(8): 1125–1131.