Does Parkinson’s Disease Originate in the Gut?

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Parkinson’s disease (PD) is the most common serious movement disorder and second most common neurodegenerative disorder in the world (the first being Alzheimer’s disease).1,2 PD involves loss of neurons in the specific area of the brain that controls motor movement—the substantia nigra.

Parkinson’s disease involves the gradual death of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies, or protein accumulations, in the remaining neurons. Lewy bodies have been associated with the destruction of brain cells in Parksinson’s disease.

Parkinson’s is diagnosed by the presence of motor symptoms including tremor (shaking) at rest, bradykinesia (slowness of movement), rigidity (stiffness, cramps, or aches and pains), and postural instability (loss of balance). Early in the disease, however, diagnosis is difficult, with 10 to 20 percent of patients being misdiagnosed.3

Researchers involved in an interesting study recently published in the journal Movement Disorders, continued, “The diagnostic opportunity occurs relatively late in the evolution of PD pathology, when there is already significant cell loss. Estimates are that the characteristic motor signs do not appear until the midbrain degenerative process is well advanced, with loss of as many as 40 to 60 percent of dopaminergic neurons at the onset of motor symptoms.”

This study is interesting because it found that people with Parkinson’s had an accumulation of alpha-synuclein (a major component of Lewy bodies) in their large intestines as found through biopsy during colonoscopy.4 The researchers stated, “Clinical and clinicopathological data support the concept that the gastrointestinal tract might be a portal of pathogen entry in at least some patients with PD.” They continue to make the gut-brain connection by noting, “PD patients often report long-standing constipation, which begins before motor signs in nearly half of all PD subjects and predates motor signs by 12 to 18 years.”

In the brains of people with Parkinson’s, Lewy bodies first accumulate in the dorsal motor nucleus, an area of the brain that is directly connected to the gastrointestinal tract. Because of this, previous researchers have hypothesized that Parkinson’s disease could theoretically originate in the gut.5 In another previous epidemiological study of more than 8000 Hawaiian men of Japanese ancestry, those men with fewer bowel movements had a higher risk of PD compared with men who had normal bowel function.6

I bet we will soon find out that the alpha-synuclein occurs in response to some microbial vectors, likely viruses, much the same way the beta amyloid in Alzheimer’s occurs in response to many microbial vectors. Beta amyloid is now thought to be an intracellular antimicrobial produced in response to several different viruses. Alpha-synuclein may be something similar.

So here we have this Alpha-synuclein throughout the colon and maybe even in the stomach, which if it is an immune response to, or biomarker of, microbial invasion,7 it could be just a matter of time before this microbial “stealth” invasion attacks several areas of the brain either sequentially or simultaneously. And depending on individual variation, PD symptoms may come sooner or later. Studies have already found a link between ulcers of the stomach or upper small intestine (duodenum), suggesting H. pylori—the bacterium most often causing these ulcers—may be involved in the development of PD.8,9

Could alpha-synuclein, as detected through a simple (non-bowel-prepped) colonoscopy, be a biomarker for future development on Parkinson’s disease? Does Parkinson’s disease originate in the gut? We can’t yet know for sure, but we do know that there is an important gut connection to Parkinson’s disease. This study is promising, and more studies will be needed to determine whether this test can improve our current practice for diagnosis and treatment of this difficult disease. In the meantime, constipation is a condition that should be addressed in everyone, for even more reasons than its connection to Parkinson’s disease. Optimal elimination means at least one healthy bowel movement daily. Have you achieved bowel regularity yet? If not, try the HOPE Formula—High fiber, Omega-3 Oils, Probiotics, and digestive Enzymes.

References

  1. A.J. Lees, et al., “Parkinson’s Disease.” Lancet. 13 June 2009;373(9680):2055–55.
  2. R.L. Nussbun and C.E. Ellis, “Alzheimer’s disease and Parkinson’s disease.” N Eng J Med. 3 Apr 2003;348(14):1356–64.
  3. A.J. Hughes, et al., “Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases.” J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181–4.
  4. K.M. Shannon, et al., “Alpha-synuclein in colonic submucosa in early untreated Parkinson’s disease.” Mov Disord. 2012 May;27(6):709–15.
  5. C.W. Olanow, “A colonic biomarker of Parkinson’s disease?” Mov Disord. 2012 May;27(6):674–6.
  6. R.D. Abbott, et al., “Frequency of bowel movements and the future risk of Parkinson’s disease.” Neurology. 2001 Aug 14;57(3):456–62.
  7. H. Braak, et al., “Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen.” J Neural Transm. 2003 May;110(5):517–36.
  8. R.R. Strang, “The association of gastro-duodenal ulceration and Parkinson’s disease.” Med J Aust. 1965;1:842–843.
  9. E. Altschuler, “Gastric Helicobacter pylori infection as a cause of idiopathic Parkinson disease and non-arteric anterior optic ischemic neuropathy.” Med Hypotheses. 1996 Nov;47(5):413–4.

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