An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS.
Tau protein is a key target of interest in developing therapeutics for neurodegenerative diseases. Here, we sought to develop a method that quantifies extracellular tau protein concentrations in human cerebrospinal fluid (CSF) without antibody-based enrichment strategies. We demonstrate that the fit...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0269157 |
| _version_ | 1811289744026370048 |
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| author | Wade Self Khader Awwad John Paul Savaryn Michael Schulz |
| author_facet | Wade Self Khader Awwad John Paul Savaryn Michael Schulz |
| author_sort | Wade Self |
| collection | DOAJ |
| description | Tau protein is a key target of interest in developing therapeutics for neurodegenerative diseases. Here, we sought to develop a method that quantifies extracellular tau protein concentrations in human cerebrospinal fluid (CSF) without antibody-based enrichment strategies. We demonstrate that the fit-for-purpose validated method in Alzheimer's Disease CSF is limited to quasi quantitative measures of tau surrogate peptides. We also provide evidence that CSF total Tau measures by LC-MS are feasible in the presence of monoclonal therapeutic antibodies in human CSF. Our Tau LC-MS/MS method is a translational bioanalytical tool for assaying target engagement and pharmacodynamics for anti-tau antibody drug development campaigns. |
| first_indexed | 2024-04-13T04:00:54Z |
| format | Article |
| id | doaj.art-50a4e3e212e143dd8ace87036d009ac9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T04:00:54Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-50a4e3e212e143dd8ace87036d009ac92022-12-22T03:03:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01176e026915710.1371/journal.pone.0269157An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS.Wade SelfKhader AwwadJohn Paul SavarynMichael SchulzTau protein is a key target of interest in developing therapeutics for neurodegenerative diseases. Here, we sought to develop a method that quantifies extracellular tau protein concentrations in human cerebrospinal fluid (CSF) without antibody-based enrichment strategies. We demonstrate that the fit-for-purpose validated method in Alzheimer's Disease CSF is limited to quasi quantitative measures of tau surrogate peptides. We also provide evidence that CSF total Tau measures by LC-MS are feasible in the presence of monoclonal therapeutic antibodies in human CSF. Our Tau LC-MS/MS method is a translational bioanalytical tool for assaying target engagement and pharmacodynamics for anti-tau antibody drug development campaigns.https://doi.org/10.1371/journal.pone.0269157 |
| spellingShingle | Wade Self Khader Awwad John Paul Savaryn Michael Schulz An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS. PLoS ONE |
| title | An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS. |
| title_full | An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS. |
| title_fullStr | An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS. |
| title_full_unstemmed | An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS. |
| title_short | An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS. |
| title_sort | immuno enrichment free validated quantification of tau protein in human csf by lc ms ms |
| url | https://doi.org/10.1371/journal.pone.0269157 |
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