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Colonoscopy May Detect Early Parkinsonís Disease

In the future, doctors may be able to diagnose early Parkinson’s disease (PD) with a colonoscopy, suggests a new study funded in part by the Parkinson’s Disease Foundation (PDF) and published in the journal Movement Disorders.  In the future, early diagnosis — before a person actually experiences symptoms of the disease — may enable more effective treatment of PD.

Currently, doctors diagnose PD by observing symptoms such as tremor, slowed movements, and impaired balance.  Yet because these symptoms can also occur in other disorders, up to 20 percent of suspected cases of PD are misdiagnosed.  In addition, most people with PD don’t show symptoms until they have lost the function of 60 to 80 percent of the dopamine-producing cells in the brain.  If doctors could detect PD at earlier stages, they might be able to slow or prevent the loss of dopamine-producing cells.

In people with PD, the α-synuclein protein forms abnormal clumps in cells, and these toxic aggregates kill dopamine-producing neurons.  Scientists have also detected α-synuclein aggregates in other cells of the body, including nerve cells of the colon and skin of people with PD.  One hypothesis is that the disease actually begins in tissues outside the brain, and α-synuclein aggregates pass from cell to cell until they reach the central nervous system.

Kathleen Shannon, M.D., and her colleagues at the PDF Research Center at Rush University Medical Center wondered whether the presence of α-synuclein aggregating in colon tissue could predict PD development years later.  So they studied old colon biopsy samples from three people with PD.  The biopsies were collected by a colonoscopy two to five years before the people began showing symptoms of PD.  The researchers detected α-synuclein in the colon tissue samples by staining the protein with specific dyes or fluorescent molecules.

Results

  • α-Synuclein protein was detected in nerve cells of colon tissue from all three people who later developed symptoms of PD.
  • No α-synuclein was detected in colon tissue samples from 23 healthy people without PD.

What Does It Mean?

Accumulating evidence suggests that PD may actually begin in neurons of the intestinal wall and spread by cell-to-cell transfer of α-synuclein through the vagus nerve to the brain.  In support of this hypothesis, Dr. Shannon and her coworkers detected α-synuclein in colon tissue samples removed two to five years before people reported any symptoms of PD. This study is the first to demonstrate α-synuclein aggregation in colon tissue before the onset of motor symptoms of PD.

If the findings from this very small study are replicated in a larger number of samples, these results suggest that in the future, it may be possible to use colonoscopy to predict who will develop PD.  Doctors already recommend that people age 50 and older have a colonoscopy every three to ten years for colon cancer surveillance.  For those who would be interested the same biopsy may be able to predict their risk for PD.  Therefore, it would be relatively easy to test colon tissue biopsies for both cancer and α-synuclein protein.  Alternatively, a less invasive procedure called flexible sigmoidoscopy can obtain tissue from the lower intestine in about 10 minutes, without colon cleansing preparation or sedation.  However, researchers need to determine which areas of the colon will most likely contain the most α-synuclein for testing before they can gauge the suitability of flexible sigmoidoscopy for PD prediction.

Early detection of PD, before the significant loss of dopamine-producing neurons, would help facilitate a search for a cure, or for interventions that slow disease prevention.  People with an increased risk of developing PD — for example, relatives of people with PD — would especially benefit from a method for early diagnosis.  Although these initial results are promising, it will be important to confirm the results in larger populations of people with and without PD, as well as people with Parkinson’s-like disorders.

Reference: Shannon, K. M., Keshavarzian, A., Dodiya, H. B., Jakate, S., & Kordower, J. H. (2012). Is alpha-synuclein in the colon a biomarker for premotor Parkinson's Disease? Evidence from 3 cases. Movement disorders. Epub Ahead of Print. doi:10.1002/mds.25020

Source Date: Jun 01 2012