Immunoassay detection of multiphosphorylated tau proteoforms as cerebrospinal fluid and plasma Alzheimer’s disease biomarkers
Abstract Different forms of phosphorylated tau (p-tau) have shown strong potential as Alzheimer’s disease (AD) biomarkers in both cerebrospinal fluid (CSF) and plasma. We hypothesized that p-tau proteoforms simultaneously phosphorylated at two different sites may have an increased diagnostic value c...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54878-8 |
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| author | Anna L. Wojdała Giovanni Bellomo Lorenzo Gaetani Charlotte E. Teunissen Lucilla Parnetti Davide Chiasserini |
| author_facet | Anna L. Wojdała Giovanni Bellomo Lorenzo Gaetani Charlotte E. Teunissen Lucilla Parnetti Davide Chiasserini |
| author_sort | Anna L. Wojdała |
| collection | DOAJ |
| description | Abstract Different forms of phosphorylated tau (p-tau) have shown strong potential as Alzheimer’s disease (AD) biomarkers in both cerebrospinal fluid (CSF) and plasma. We hypothesized that p-tau proteoforms simultaneously phosphorylated at two different sites may have an increased diagnostic value compared with tau phosphorylated at a single site. Here, we developed two immunoassays detecting CSF and plasma tau simultaneously phosphorylated at both T181 and T231 (p-tau181&231) and at T217 and T231 (p-tau217&231). Subsequently, we measured CSF and plasma p-tau181&231, p-tau217&231, p-tau181, p-tau217, and p-tau231 levels in two cohorts across the AD continuum and in frontotemporal dementia (FTD) patients (discovery n = 55, validation n = 118). CSF and plasma p-tau217&231, p-tau181, p-tau217, and p-tau231 and CSF, but not plasma, p-tau181&231 were significantly elevated in all AD continuum groups vs. Neurological Disease Control group. Notably, plasma p-tau217&231 consistently showed an improved diagnostic performance compared with single-site phosphorylation assays – p-tau217 or p-tau231. The differences observed between CSF and plasma measurements suggest matrix-specific protein processing, underscoring the need for further research on the dynamics of tau phosphorylation pattern along the AD continuum. |
| format | Article |
| id | doaj-art-c4957a89513546c38d3ce49ab17af115 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-c4957a89513546c38d3ce49ab17af1152025-01-05T12:37:49ZengNature PortfolioNature Communications2041-17232025-01-0116111110.1038/s41467-024-54878-8Immunoassay detection of multiphosphorylated tau proteoforms as cerebrospinal fluid and plasma Alzheimer’s disease biomarkersAnna L. Wojdała0Giovanni Bellomo1Lorenzo Gaetani2Charlotte E. Teunissen3Lucilla Parnetti4Davide Chiasserini5Laboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery, University of PerugiaLaboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery, University of PerugiaLaboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery, University of PerugiaNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam UMCLaboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery, University of PerugiaSection of Physiology and Biochemistry, Department of Medicine and Surgery, University of PerugiaAbstract Different forms of phosphorylated tau (p-tau) have shown strong potential as Alzheimer’s disease (AD) biomarkers in both cerebrospinal fluid (CSF) and plasma. We hypothesized that p-tau proteoforms simultaneously phosphorylated at two different sites may have an increased diagnostic value compared with tau phosphorylated at a single site. Here, we developed two immunoassays detecting CSF and plasma tau simultaneously phosphorylated at both T181 and T231 (p-tau181&231) and at T217 and T231 (p-tau217&231). Subsequently, we measured CSF and plasma p-tau181&231, p-tau217&231, p-tau181, p-tau217, and p-tau231 levels in two cohorts across the AD continuum and in frontotemporal dementia (FTD) patients (discovery n = 55, validation n = 118). CSF and plasma p-tau217&231, p-tau181, p-tau217, and p-tau231 and CSF, but not plasma, p-tau181&231 were significantly elevated in all AD continuum groups vs. Neurological Disease Control group. Notably, plasma p-tau217&231 consistently showed an improved diagnostic performance compared with single-site phosphorylation assays – p-tau217 or p-tau231. The differences observed between CSF and plasma measurements suggest matrix-specific protein processing, underscoring the need for further research on the dynamics of tau phosphorylation pattern along the AD continuum.https://doi.org/10.1038/s41467-024-54878-8 |
| spellingShingle | Anna L. Wojdała Giovanni Bellomo Lorenzo Gaetani Charlotte E. Teunissen Lucilla Parnetti Davide Chiasserini Immunoassay detection of multiphosphorylated tau proteoforms as cerebrospinal fluid and plasma Alzheimer’s disease biomarkers Nature Communications |
| title | Immunoassay detection of multiphosphorylated tau proteoforms as cerebrospinal fluid and plasma Alzheimer’s disease biomarkers |
| title_full | Immunoassay detection of multiphosphorylated tau proteoforms as cerebrospinal fluid and plasma Alzheimer’s disease biomarkers |
| title_fullStr | Immunoassay detection of multiphosphorylated tau proteoforms as cerebrospinal fluid and plasma Alzheimer’s disease biomarkers |
| title_full_unstemmed | Immunoassay detection of multiphosphorylated tau proteoforms as cerebrospinal fluid and plasma Alzheimer’s disease biomarkers |
| title_short | Immunoassay detection of multiphosphorylated tau proteoforms as cerebrospinal fluid and plasma Alzheimer’s disease biomarkers |
| title_sort | immunoassay detection of multiphosphorylated tau proteoforms as cerebrospinal fluid and plasma alzheimer s disease biomarkers |
| url | https://doi.org/10.1038/s41467-024-54878-8 |
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