...and worth every penny.

There is a more detailed outline at http://www.parkinsonsonline.org/PD_Outline_Index.html, but the condensed version is an overlapping interaction of abnormal ("dysregulated") states in the immune, endocrine, and GI systems impacting the nervous system. The damage we see in the SN etc is a symptom of the real causes and that is why the new cells die.

Given the pattern of PD in the population, certain requirements are going to have to be met by any explanation. Family clusters are rare, so it is not pure genetics. Environmental toxins would produce a pattern of localized case "clumping" that is not seen. It appears to be increasing and appearing at a younger age.It seems more prevalent in the industrialized West. And, despite the common wisdom, it seems to have been a rare affliction prior to James Parkinson' s essay. Even his description is significantly different than what we experience. And reading the so-called "ancient texts" that purportedly describe the condition is less than convincing. They could be describing many things.

The cause must be common but the effect rare. Still with me? Darn, I like that sentence. It is paradoxical just like PD.

Common because PD is found all over the world and rare because only we lucky few get it. Think of an inverse Lotto game. Everybody's buying tickets but only a few win the prize.

Expose a fetus or young child to bacterial toxin LPS and his immune system becomes sensitized or "primed" against further encounters.

Expose the same child to stress hormones and he becomes sensitized to them. In addition, his control system for such things becomes out of whack.

Much of the effects of both exposures don't show up until after puberty.

Stress chemicals slow the GI system. The immune system and the stress (endocrine) system both cause inflammation which, in turn, causes both "leaky gut" and a leaky BBB.

This leads to toxins from the GI system finding their way to the brain. One of the most common is LPS. Within the brain, LPS triggers the "innate" immune warriors, the microglia. Already "primed", they over react and release chemicals (cytokines) that do collateral damage to neurons. (BTW, the substantia nigra has one of the highest densities of microglia in the brain.)

In addition, the chemical soup from chronic stress kills neurons. It also interferes with neurogenic repair.

So, our neurons are bathed in a mix of three soups. The toxins that escape from the GI tract. The one that comes from the immune system. And the third from the endocrine system. Each leading to dead neurons.

And that is the condensed version.

For the record, 75% of that comes from the work of our ocassional guest Anne Frobert, MD.