A recent article has re-ignited the debate on the role of the gastro-intestinal tract in the earliest stages of Parkinson’s and whether tissue biopsies routinely taken during gastroscopy or colonoscopy tests could be used to help diagnose the disease. Hilton et al analysed 117 previously collected samples of gut using antibodies against abnormal alpha-synuclein protein. This marker of disease could be detected in samples taken up to 8 years before the diagnosis of Parkinson’s was made. This adds weight to the ‘Braak Hypothesis’ that the disease process could begin in the gastrointestinal tract before affecting the brain, however, it also supports the emerging idea that gastrointestinal tissue samples could help diagnose early Parkinson’s (or at least identify people who could go on to develop the disease). This is clearly a fascinating area of Parkinson’s research however these markers of disease could only be found in a minority of patients and more work is needed to determine if such tests can reliably detect the disease in the general population.
Acta Neuropathologica, 17th November 2013.
Abstract: Parkinson's disease primarily affects the central nervous system, but autopsy and small patient studies have revealed autonomic nervous system pathology in most cases. We looked for α-synuclein pathology in routinely acquired biopsies from patients and matched controls. Immunocytochemistry was performed and assessed blind to the clinical diagnoses. One hundred and seventeen gastrointestinal tissue samples from 62 patients, and 161 samples from 161 controls, were examined. Twelve biopsies from seven patients showed accumulation of α-synuclein within mucosal and submucosal nerve fibres, and ganglia, which was more extensive with an antibody to phosphorylated, than with an antibody to non-phosphorylated, α-synuclein. These included gastric, duodenal and colonic biopsies, and were taken up to 8 years prior to the onset of motor symptoms. All patients with positive biopsies had early autonomic symptoms and all controls were negative. This large scale study demonstrates that accumulation of α-synuclein in the gastrointestinal tract is a highly specific finding that could be used to confirm a clinical diagnosis of Parkinson's disease. We have shown that α-synuclein accumulation occurs prior to the onset of motor symptoms in the upper, as well as the lower gastrointestinal tract, remains present in serial biopsies until the onset of motor symptoms and is predominantly composed of phosphorylated α-synuclein. Accumulation of α-synuclein in the bowel therefore offers an accessible biomarker which allows further study of the early stages of the disease and could be of value in the assessment of disease modifying treatments.
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