Colonic mucosal α-synuclein lacks specificity as a biomarker for Parkinson disease
Identifieur interne : 000792 ( Main/Exploration ); précédent : 000791; suivant : 000793Colonic mucosal α-synuclein lacks specificity as a biomarker for Parkinson disease
Auteurs : Naomi P. Visanji ; Connie Marras ; Drew S. Kern ; Amaal Al Dakheel ; Andrew Gao ; Louis W. C. Liu ; Anthony E. Lang ; Lili-Naz HazratiSource :
- Neurology [ 0028-3878 ] ; 2015.
Abstract
To determine the utility of detecting α-synuclein (αSyn) in colonic mucosal biopsy tissue as a potential diagnostic biomarker for Parkinson disease (PD).
We used the paraffin-embedded tissue (PET) blot, which degrades physiologic nonaggregated αSyn using proteinase K and enhances antigen retrieval allowing sensitive and selective detection of remaining protein aggregates, to detect αSyn in colonic mucosal biopsies from 15 patients with early PD (<3 years), 7 patients with later PD (>5 years), and 11 individuals without PD. αSyn and serine 129–phosphorylated αSyn (Ser129p-αSyn) were assessed by PET blot and conventional immunohistochemistry.
PET blot–resistant aggregated αSyn and Ser129p-αSyn was present in 12 of 15 individuals with early PD, 7 of 7 individuals with later PD, and 11 of 11 control subjects. The number of biopsies positive by PET blot relative to conventional immunohistochemistry was significantly lower in both PD groups compared with the control group for both αSyn and Ser129p-αSyn, whereas routine immunohistochemistry was positive more often in PD, but was positive in as many as 9 of 11 control individuals.
Strong evidence of the presence of aggregated hyperphosphorylated αSyn in individuals with and without PD, using such a sensitive and specific method as the PET blot, suggests that colonic deposition of αSyn is not a useful diagnostic test for PD. The utility of detecting αSyn in the colon as a biomarker in combination with other assessments remains to be determined.
Url:
DOI: 10.1212/WNL.0000000000001240
PubMed: 25589666
PubMed Central: 4335990
Affiliations:
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Liu</name></author><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name></author><author><name sortKey="Hazrati, Lili Naz" sort="Hazrati, Lili Naz" uniqKey="Hazrati L" first="Lili-Naz" last="Hazrati">Lili-Naz Hazrati</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25589666</idno><idno type="pmc">4335990</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335990</idno><idno type="RBID">PMC:4335990</idno><idno type="doi">10.1212/WNL.0000000000001240</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000622</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000622</idno><idno type="wicri:Area/Pmc/Curation">000622</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000622</idno><idno type="wicri:Area/Pmc/Checkpoint">000340</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000340</idno><idno type="wicri:Area/Ncbi/Merge">001A37</idno><idno type="wicri:Area/Ncbi/Curation">001A37</idno><idno type="wicri:Area/Ncbi/Checkpoint">001A37</idno><idno type="wicri:doubleKey">0028-3878:2015:Visanji N:colonic:mucosal:synuclein</idno><idno type="wicri:Area/Main/Merge">000793</idno><idno type="wicri:Area/Main/Curation">000792</idno><idno type="wicri:Area/Main/Exploration">000792</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Colonic mucosal α-synuclein lacks specificity as a biomarker for Parkinson disease</title><author><name sortKey="Visanji, Naomi P" sort="Visanji, Naomi P" uniqKey="Visanji N" first="Naomi P." last="Visanji">Naomi P. Visanji</name></author><author><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name></author><author><name sortKey="Kern, Drew S" sort="Kern, Drew S" uniqKey="Kern D" first="Drew S." last="Kern">Drew S. Kern</name></author><author><name sortKey="Al Dakheel, Amaal" sort="Al Dakheel, Amaal" uniqKey="Al Dakheel A" first="Amaal" last="Al Dakheel">Amaal Al Dakheel</name></author><author><name sortKey="Gao, Andrew" sort="Gao, Andrew" uniqKey="Gao A" first="Andrew" last="Gao">Andrew Gao</name></author><author><name sortKey="Liu, Louis W C" sort="Liu, Louis W C" uniqKey="Liu L" first="Louis W. C." last="Liu">Louis W. C. Liu</name></author><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name></author><author><name sortKey="Hazrati, Lili Naz" sort="Hazrati, Lili Naz" uniqKey="Hazrati L" first="Lili-Naz" last="Hazrati">Lili-Naz Hazrati</name></author></analytic><series><title level="j">Neurology</title><idno type="ISSN">0028-3878</idno><idno type="eISSN">1526-632X</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objective:</title><p>To determine the utility of detecting α-synuclein (αSyn) in colonic mucosal biopsy tissue as a potential diagnostic biomarker for Parkinson disease (PD).</p></sec><sec><title>Methods:</title><p>We used the paraffin-embedded tissue (PET) blot, which degrades physiologic nonaggregated αSyn using proteinase K and enhances antigen retrieval allowing sensitive and selective detection of remaining protein aggregates, to detect αSyn in colonic mucosal biopsies from 15 patients with early PD (<3 years), 7 patients with later PD (>5 years), and 11 individuals without PD. αSyn and serine 129–phosphorylated αSyn (Ser129p-αSyn) were assessed by PET blot and conventional immunohistochemistry.</p></sec><sec><title>Results:</title><p>PET blot–resistant aggregated αSyn and Ser129p-αSyn was present in 12 of 15 individuals with early PD, 7 of 7 individuals with later PD, and 11 of 11 control subjects. The number of biopsies positive by PET blot relative to conventional immunohistochemistry was significantly lower in both PD groups compared with the control group for both αSyn and Ser129p-αSyn, whereas routine immunohistochemistry was positive more often in PD, but was positive in as many as 9 of 11 control individuals.</p></sec><sec><title>Conclusion:</title><p>Strong evidence of the presence of aggregated hyperphosphorylated αSyn in individuals with and without PD, using such a sensitive and specific method as the PET blot, suggests that colonic deposition of αSyn is not a useful diagnostic test for PD. The utility of detecting αSyn in the colon as a biomarker in combination with other assessments remains to be determined.</p></sec></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Al Dakheel, Amaal" sort="Al Dakheel, Amaal" uniqKey="Al Dakheel A" first="Amaal" last="Al Dakheel">Amaal Al Dakheel</name><name sortKey="Gao, Andrew" sort="Gao, Andrew" uniqKey="Gao A" first="Andrew" last="Gao">Andrew Gao</name><name sortKey="Hazrati, Lili Naz" sort="Hazrati, Lili Naz" uniqKey="Hazrati L" first="Lili-Naz" last="Hazrati">Lili-Naz Hazrati</name><name sortKey="Kern, Drew S" sort="Kern, Drew S" uniqKey="Kern D" first="Drew S." last="Kern">Drew S. Kern</name><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name><name sortKey="Liu, Louis W C" sort="Liu, Louis W C" uniqKey="Liu L" first="Louis W. C." last="Liu">Louis W. C. Liu</name><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name><name sortKey="Visanji, Naomi P" sort="Visanji, Naomi P" uniqKey="Visanji N" first="Naomi P." last="Visanji">Naomi P. Visanji</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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