Diagnosing Parkinson’s via GI Tract May Require More Extensive Biopsy | Wider Array of Tissue Samples Better Spot Protein Clumping

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A more extensive biopsy involving larger tissue samples taken from the gastrointestinal (GI) tract of people with Parkinson’s disease improves the ability to identify alpha-synuclein protein clumping, researchers in a small study reported.

These findings support more extensive GI biopsies as a diagnostic tool for Parkinson’s and other conditions related to alpha-synuclein, while highlighting the complexities of such diseases.

The work,”Sensitivity of Detecting Alpha-Synuclein Accumulation in the Gastrointestinal Tract and Tissue Volume Examined,” was published as a brief communication in the Journal of Movement Disorders.

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In Parkinson’s, the clumping of alpha-synuclein protein is thought to cause the loss of cells that produce dopamine, a nerve signaling molecule or neurotransmitter. The subsequent drop in dopamine levels leads to various motor and nonmotor symptoms.

Digestive tract and diagnosing Parkinson’s

Problems with the GI tract, such as blockages that result in cramping, abdominal pain, constipation, vomiting, and bloating, are among the disorder’s nonmotor symptoms.

Detecting alpha-synuclein accumulation in the gut has the potential to be a biomarker for diagnosing Parkinson’s. However, biopsies of GI tissue lack the degree of high sensitivity — the ability to correctly identify those with this disease — to be a reliable tool in the clinic.

While studies have shown that multiple sections of thinly sliced ​​tissue improved the positivity rate, others indicated that whole-mount staining, or the staining of small pieces of tissue without thin slicing, reported a higher sensitivity.

These divergent findings prompted researchers at Chungnam National University College of Medicine in Korea to determine whether a larger tissue volume would increase the sensitivity of detecting alpha-synuclein disease in the digestive tract.

They analyzed biopsy samples collected from nine patients and five healthy people serving as controls.

Among the patients, four were diagnosed with Parkinson’s, and five had idiopathic rapid eye movement sleep behavior disorder (iRBD) — a condition marked by unusual movements and behaviors while sleeping. iRBD is strongly linked to diseases related to alpha-synuclein accumulation and is a common Parkinson’s symptom.

Two blocks of tissue from the upper (proximal) and lower (distal) part of either the esophagus, stomach, or upper colon were biopsied. Five serial sections, meaning thin slices, were obtained from each block for a total of 10 serial sections per person. Each section was then mounted on a microscope slide and stained with an alpha-synuclein-specific antibody for examination.

Previous analysis of these tissue samples was positive for alpha-synuclein accumulation in five out of nine patient samples (55.6%) and one control (20%).

Extending the analysis to 10 slides per person identified alpha-synuclein accumulation in eight out of the nine patients (88.9%) and one control (20%).

Further examination of the five sections showed six patients (66.7%) were positive for alpha-synuclein in both areas (proximal and distal) of their respective tissue samples.

“These results further support the fundamental limit of biopsies that contain only a small portion of mucosal and submucosal layers from the intestinal wall,” the researchers reported.

Alpha-synuclein was present in all five serial sections in 12 out of 15 (80%) tissue blocks staining positive for one patient and one control, while their remaining three blocks were the exceptions.

More intense staining, meaning more alpha-synuclein accumulation, was found in both Parkinson’s and iRBD patients. When differences were seen between proximal and distal samples, in two patients and one control, mild staining density was found. Further, mild staining density still occurred when positive samples were not observed across all five serial sections.

“Examination of a large tissue volume increased the sensitivity of detection [alpha-synuclein] accumulation in the GI tract,” the researchers concluded. “This study implies a fundamental limit of biopsied tissue and highlights the complexity of pathologic progression of synucleinopathy. [alpha-synuclein diseases].”

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