An enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function.
<h4>Objective</h4>Alzheimer's disease (AD) is a devastating neurological disease characterized by pathological proteolytic cleavage of tau protein, which appears to initiate death of the neurons. The objective of this study was to investigate whether a proteolytic fragment of the ta...
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2013
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oai:doaj.org-article:2b6f9215175d48329c9c1c6a33b5e3972021-11-18T07:44:29ZAn enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function.1932-620310.1371/journal.pone.0064990https://doaj.org/article/2b6f9215175d48329c9c1c6a33b5e3972013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23717682/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>Alzheimer's disease (AD) is a devastating neurological disease characterized by pathological proteolytic cleavage of tau protein, which appears to initiate death of the neurons. The objective of this study was to investigate whether a proteolytic fragment of the tau protein could serve as blood-based biomarker of cognitive function in AD.<h4>Methods</h4>We developed a highly sensitive ELISA assay specifically detecting an A Disintegrin and Metalloproteinase 10 (ADAM10)-generated fragment of tau (Tau-A). We characterized the assay in detail with to respect specificity and reactivity in healthy human serum. We used samples from the Tg4510 tau transgenic mice, which over-express the tau mutant P301L and exhibit a tauopathy with similarities to that observed in AD. We used serum samples from 21 well-characterized Alzheimer's patients, and we correlated the Tau-A levels to cognitive function.<h4>Results</h4>The Tau-A ELISA specifically detected the cleavage sequence at the N-terminus of a fragment of tau generated by ADAM10 with no cross-reactivity to intact tau or brain extracts. In brain extracts from Tg4510 mice compared to wt controls we found 10-fold higher levels of Tau-A (p<0.001), which indicates a pathological relevance of this marker. In serum from healthy individuals we found robust and reproducible levels of Tau-A, indicating that the analyte is present in serum. In serum from AD patients an inverse correlation (R² = 0.46, p<0.001) between the cognitive assessment score (Mattis Dementia Rating Scale (MDRS)) and Tau-A levels was observed.<h4>Conclusion</h4>Based on the hypothesis that tau is cleaved proteolytically and then released into the blood, we here provide evidence for the presence of an ADAM10-generated tau fragment (Tau-A) in serum. In addition, the levels of Tau-A showed an inverse correlation to cognitive function, which could indicate that this marker is a serum marker with pathological relevance for AD.Kim HenriksenYaguo WangMette G SørensenNatasha BarascukJoyce SuhyJan T PedersenKevin L DuffinRobert A DeanMonika PajakClaus ChristiansenQinlong ZhengMorten A KarsdalPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e64990 (2013) |
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Medicine R Science Q Kim Henriksen Yaguo Wang Mette G Sørensen Natasha Barascuk Joyce Suhy Jan T Pedersen Kevin L Duffin Robert A Dean Monika Pajak Claus Christiansen Qinlong Zheng Morten A Karsdal An enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function. |
| description |
<h4>Objective</h4>Alzheimer's disease (AD) is a devastating neurological disease characterized by pathological proteolytic cleavage of tau protein, which appears to initiate death of the neurons. The objective of this study was to investigate whether a proteolytic fragment of the tau protein could serve as blood-based biomarker of cognitive function in AD.<h4>Methods</h4>We developed a highly sensitive ELISA assay specifically detecting an A Disintegrin and Metalloproteinase 10 (ADAM10)-generated fragment of tau (Tau-A). We characterized the assay in detail with to respect specificity and reactivity in healthy human serum. We used samples from the Tg4510 tau transgenic mice, which over-express the tau mutant P301L and exhibit a tauopathy with similarities to that observed in AD. We used serum samples from 21 well-characterized Alzheimer's patients, and we correlated the Tau-A levels to cognitive function.<h4>Results</h4>The Tau-A ELISA specifically detected the cleavage sequence at the N-terminus of a fragment of tau generated by ADAM10 with no cross-reactivity to intact tau or brain extracts. In brain extracts from Tg4510 mice compared to wt controls we found 10-fold higher levels of Tau-A (p<0.001), which indicates a pathological relevance of this marker. In serum from healthy individuals we found robust and reproducible levels of Tau-A, indicating that the analyte is present in serum. In serum from AD patients an inverse correlation (R² = 0.46, p<0.001) between the cognitive assessment score (Mattis Dementia Rating Scale (MDRS)) and Tau-A levels was observed.<h4>Conclusion</h4>Based on the hypothesis that tau is cleaved proteolytically and then released into the blood, we here provide evidence for the presence of an ADAM10-generated tau fragment (Tau-A) in serum. In addition, the levels of Tau-A showed an inverse correlation to cognitive function, which could indicate that this marker is a serum marker with pathological relevance for AD. |
| format |
article |
| author |
Kim Henriksen Yaguo Wang Mette G Sørensen Natasha Barascuk Joyce Suhy Jan T Pedersen Kevin L Duffin Robert A Dean Monika Pajak Claus Christiansen Qinlong Zheng Morten A Karsdal |
| author_facet |
Kim Henriksen Yaguo Wang Mette G Sørensen Natasha Barascuk Joyce Suhy Jan T Pedersen Kevin L Duffin Robert A Dean Monika Pajak Claus Christiansen Qinlong Zheng Morten A Karsdal |
| author_sort |
Kim Henriksen |
| title |
An enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function. |
| title_short |
An enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function. |
| title_full |
An enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function. |
| title_fullStr |
An enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function. |
| title_full_unstemmed |
An enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function. |
| title_sort |
enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/2b6f9215175d48329c9c1c6a33b5e397 |
| work_keys_str_mv |
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