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If nothing else, PD is a fascinating puzzle. There is almost nothing that explains it that is not provisional. Even the question of genetic contribution is challenged by epigenetics (Lamarck's ghost has a laugh). I have written a book (I know. I know. Who hasn't? ;-) that is a little out of date but still worth reading. Available free and worth every penny at http://www.parkinsonsonline.org/forum1/viewtopic.php?f=239&t=208 My own view, based on peer reviewed work, is as follows: 1) Bin Liu and J.S.Hong at the NIH and P.M. Carvey at Rush have explored what happens to a rat exposed to the byproducts of maternal infection such as vaginosis or periodontal disease. The byproducts are endotoxins (lipopolysaccharide or LPS) and they affect the rat pup in ways that point to PD- reduced neuronal density in the SN for one. But the big one is the sensitization of the immune system leading to activation of the microglia in the brain. This leads to neuronal loss due to neuroinflammation and eventually motor symptoms. 2) The same exposure also disrupts the fetal endocrine system, particularly the stress circuit of the hypothalamus-pituitary-adrenal axis. It is poorly controlled in the adult or "dysregulated." 3) Inflammation (as in #1) is controlled by the HPA (#2) by the release of natural steroids, primarily cortisol. But since the inflammation is a chronic condition, the order to shut off the cortisol never is fully issued. 4) The resulting see-saw between the immune and endocrine systemsinflict neurological damage as the years go by. Further, the endocrine system begins to wear out, leading to non-motor symptoms. Agricultural dust is a heavy source of LPS, thus the hypothesis re the Amish. The exposures in #1 and #2 must occur at precise times of development of particular structures, which is why not everyone gets PD. Further stressors such as life trauma disrupts the stress element even further. There is far too much to cover here, but if anyone is interested, I would like the chance for knowledgeable feedback and discussion. It is shaping up at http://www.parkinsonsonline.org/forum1/ or here is fine if you wish. ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn