Skip to content

Research at St Andrews

Accumulation of α-synuclein in the bowel of patients in the pre-clinical phase of Parkinson's disease

Research output: Contribution to journalArticle

Author(s)

David Hilton, Madeleine Stephens, Leanne Kirk, Philip Edwards, Ross Potter, John Zajicek, Ellie Broughton, Hannah Hagan, Camille Carroll

School/Research organisations

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.

Close

Details

Original languageEnglish
Pages (from-to)235-41
Number of pages7
JournalActa Neuropathologica
Volume127
Issue number2
DOIs
Publication statusPublished - Feb 2014

    Research areas

  • Adult, Aged, Aged, 80 and over, Asymptomatic Diseases, Biomarkers, Biopsy, Case-Control Studies, Humans, Intestines, Middle Aged, Nerve Fibers, Parkinson Disease, Sensitivity and Specificity, alpha-Synuclein

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Simvastatin as a neuroprotective treatment for Parkinson's disease (PD STAT): protocol for a double-blind, randomised, placebo-controlled futility study

    Carroll, C. B., Webb, D., Stevens, K. N., Vickery, J., Eyre, V., Ball, S., Wyse, R., Webber, M., Foggo, A., Zajicek, J., Whone, A. & Creanor, S., 7 Oct 2019, In : BMJ Open. 9, 10, 11 p., e029740.

    Research output: Contribution to journalArticle

  2. Assessment of a home-based standing frame programme in people with progressive multiple sclerosis (SUMS): a pragmatic, multi-centre, randomised, controlled trial and cost-effectiveness analysis

    Freeman, J. A., Hendrie, W., Jarrett, L., Hawton, A., Barton, A., Dennett, R., Jones, B., Zajicek, J. P. & Creanor, S., 1 Aug 2019, In : Lancet Neurology. 18, 8, p. 736-747

    Research output: Contribution to journalArticle

  3. Machine-learning based identification of undiagnosed dementia in primary care: a feasibility study

    Jammeh, E. A., Carroll, C. B., Pearson, S. W., Escudero, J., Anastasiou, A., Zhao, P., Chenore, T., Zajicek, J. & Ifeachor, E., 12 Jun 2018, In : BJGP Open. 2, 2, 13 p., bjgpopen18X101589.

    Research output: Contribution to journalArticle

  4. Improving the quality of cognitive screening assessments: ACEmobile, an iPad-based version of the Addenbrooke's Cognitive Examination-III

    Newman, C. G. J., Bevins, A. D., Zajicek, J. P., Hodges, J. R., Vuillermoz, E., Dickenson, J. M., Kelly, D. S., Brown, S. & Noad, R. F., 2018, In : Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. 10, p. 182-187 6 p.

    Research output: Contribution to journalArticle

  5. Balance Right in Multiple Sclerosis (BRiMS): a guided self-management programme to reduce falls and improve quality of life, balance and mobility in people with secondary progressive multiple sclerosis: a protocol for a feasibility randomised controlled trial

    Gunn, H., Andrade, J., Paul, L., Miller, L., Creanor, S., Green, C., Marsden, J., Ewings, P., Berrow, M., Vickery, J., Barton, A., Marshall, B., Zajicek, J. & Freeman, J. A., 27 Jul 2017, In : Pilot and Feasibility Studies. 4, 12 p., 26.

    Research output: Contribution to journalArticle

Related by journal

  1. Parietal white matter lesions in Alzheimer’s disease are associated with cortical neurodegenerative pathology, but not with small vessel disease

    McAleese, K. E., Walker, L., Graham, S., Moya, E. L. J., Johnson, M., Erskine, D., Colloby, S. J., Dey, M., Martin-Ruiz, C., Taylor, J-P., Thomas, A. J., McKeith, I. G., de Carli, C. & Attems, J., Sep 2017, In : Acta Neuropathologica. 134, 3, p. 459-473 15 p.

    Research output: Contribution to journalArticle

ID: 242546374

Top