Journal article
Detection of alpha-synuclein conformational variants from gastro-intestinal biopsy tissue as a potential biomarker for Parkinson's disease
- Abstract:
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Aims
Gastrointestinal (GI) a-synuclein (aSyn) detection as a potential biomarker of Parkinson’s disease (PD) is challenged by conflicting results of recent studies. To increase sensitivity and specificity, we applied three techniques to detect different conformations of aSyn in GI biopsies obtained from a longitudinal, clinically wellcharacterized cohort of PD patients and healthy controls (HC).
Methods
With immunohistochemistry (IHC), we used antibodies reactive for total, phosphorylated and oligomeric aSyn; with aSyn proximity ligation assay (AS-PLA), we targeted oligomeric aSyn species specifically; and with paraffin-embedded tissue blot (AS-PET-blot) we aimed to detect fibrillary, synaptic aSyn.
Results
A total of 163 tissue blocks were collected from 51 PD patients (113 blocks) and 21 HC (50 blocks). In 31 PD patients, biopsies were taken before the PD diagnosis (Prodromal); while in 20 PD patients biopsies were obtained after diagnosis (Manifest). The majority of tissues blocks were from large intestine (62%), followed by small intestine (21%), stomach (10%) and oesophagus (7%). With IHC, four staining patterns were detected (neuritic, ganglionic, epithelial and cellular), while two distinct staining patterns were detected both with AS-PLA (cellular and diffuse signal) and with AS-PET-blot (aSyn-localized and pericrypt signal). The level of agreement between different techniques was low and no single technique or staining pattern reliably distinguished PD patients (Prodromal or Manifest) from HC.
Conclusions
Our study suggests that detection of aSyn conformational variants currently considered pathological is not adequate for the diagnosis or prediction of PD. Future studies utilizing novel ultrasensitive amyloid aggregation assays may increase sensitivity and specificity.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.1MB, Terms of use)
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- Publisher copy:
- 10.1111/nan.12486
Authors
- Publisher:
- Wiley
- Journal:
- Neuropathology and Applied Neurobiology More from this journal
- Volume:
- 44
- Issue:
- 7
- Pages:
- 722-736
- Publication date:
- 2018-04-19
- Acceptance date:
- 2018-04-02
- DOI:
- EISSN:
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1365-2990
- ISSN:
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0305-1846
- Pmid:
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29676021
- Language:
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English
- Keywords:
- Pubs id:
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pubs:846009
- UUID:
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uuid:1fb2ee7e-901f-455e-8986-2701fadd7dd8
- Local pid:
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pubs:846009
- Deposit date:
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2018-05-30
Terms of use
- Copyright holder:
- Parkkinen et al
- Copyright date:
- 2018
- Notes:
- © 2018 The Authors. Neuropathology and Applied Neurobiology published by John Wiley and Sons Ltd on behalf of British Neuropathological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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