P‐tau235: a novel biomarker for staging preclinical Alzheimer’s disease
Abstract Alzheimer’s disease (AD) is characterised by a long preclinical phase. Although phosphorylated tau (p‐tau) species such as p‐tau217 and p‐tau231 provide accurate detection of early pathological changes, other biomarkers capable of staging disease progression during preclinical AD are still...
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| Format: | Article |
| Language: | English |
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Springer Nature
2021-11-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202115098 |
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| author | Juan Lantero‐Rodriguez Anniina Snellman Andrea L Benedet Marta Milà‐Alomà Elena Camporesi Laia Montoliu‐Gaya Nicholas J Ashton Agathe Vrillon Thomas K Karikari Juan Domingo Gispert Gemma Salvadó Mahnaz Shekari Christina E Toomey Tammaryn L Lashley Henrik Zetterberg Marc Suárez‐Calvet Gunnar Brinkmalm Pedro Rosa Neto Kaj Blennow |
| author_facet | Juan Lantero‐Rodriguez Anniina Snellman Andrea L Benedet Marta Milà‐Alomà Elena Camporesi Laia Montoliu‐Gaya Nicholas J Ashton Agathe Vrillon Thomas K Karikari Juan Domingo Gispert Gemma Salvadó Mahnaz Shekari Christina E Toomey Tammaryn L Lashley Henrik Zetterberg Marc Suárez‐Calvet Gunnar Brinkmalm Pedro Rosa Neto Kaj Blennow |
| author_sort | Juan Lantero‐Rodriguez |
| collection | DOAJ |
| description | Abstract Alzheimer’s disease (AD) is characterised by a long preclinical phase. Although phosphorylated tau (p‐tau) species such as p‐tau217 and p‐tau231 provide accurate detection of early pathological changes, other biomarkers capable of staging disease progression during preclinical AD are still needed. Combining exploratory and targeted mass spectrometry methods in neuropathologically confirmed brain tissue, we observed that p‐tau235 is a prominent feature of AD pathology. In addition, p‐tau235 seemed to be preceded by p‐tau231, in what appeared to be a sequential phosphorylation event. To exploit its biomarker potential in cerebrospinal fluid (CSF), we developed and validated a new p‐tau235 Simoa assay. Using three clinical cohorts, we demonstrated that (i) CSF p‐235 increases early in AD continuum, and (ii) changes in CSF p‐tau235 and p‐tau231 levels during preclinical AD are consistent with the sequential phosphorylation evidence in AD brain. In conclusion, CSF p‐tau235 appears to be not only a highly specific biomarker of AD but also a promising staging biomarker for the preclinical phase. Thus, it could prove useful tracking disease progression and help enriching clinical trial recruitment. |
| format | Article |
| id | doaj-art-a5fc24b2a60148e8ada0fe84e8c1fdbc |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2021-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-a5fc24b2a60148e8ada0fe84e8c1fdbc2025-08-20T03:46:11ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842021-11-01131211610.15252/emmm.202115098P‐tau235: a novel biomarker for staging preclinical Alzheimer’s diseaseJuan Lantero‐Rodriguez0Anniina Snellman1Andrea L Benedet2Marta Milà‐Alomà3Elena Camporesi4Laia Montoliu‐Gaya5Nicholas J Ashton6Agathe Vrillon7Thomas K Karikari8Juan Domingo Gispert9Gemma Salvadó10Mahnaz Shekari11Christina E Toomey12Tammaryn L Lashley13Henrik Zetterberg14Marc Suárez‐Calvet15Gunnar Brinkmalm16Pedro Rosa Neto17Kaj Blennow18Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of GothenburgBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall FoundationDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of GothenburgCognitive Neurology Center, GHU Nord APHP Hospital Lariboisière Fernand Widal, Université de ParisDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of GothenburgBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall FoundationBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall FoundationBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall FoundationThe Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Institute of NeurologyThe Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Institute of NeurologyDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of GothenburgBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall FoundationDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of GothenburgMontreal Neurological InstituteDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of GothenburgAbstract Alzheimer’s disease (AD) is characterised by a long preclinical phase. Although phosphorylated tau (p‐tau) species such as p‐tau217 and p‐tau231 provide accurate detection of early pathological changes, other biomarkers capable of staging disease progression during preclinical AD are still needed. Combining exploratory and targeted mass spectrometry methods in neuropathologically confirmed brain tissue, we observed that p‐tau235 is a prominent feature of AD pathology. In addition, p‐tau235 seemed to be preceded by p‐tau231, in what appeared to be a sequential phosphorylation event. To exploit its biomarker potential in cerebrospinal fluid (CSF), we developed and validated a new p‐tau235 Simoa assay. Using three clinical cohorts, we demonstrated that (i) CSF p‐235 increases early in AD continuum, and (ii) changes in CSF p‐tau235 and p‐tau231 levels during preclinical AD are consistent with the sequential phosphorylation evidence in AD brain. In conclusion, CSF p‐tau235 appears to be not only a highly specific biomarker of AD but also a promising staging biomarker for the preclinical phase. Thus, it could prove useful tracking disease progression and help enriching clinical trial recruitment.https://doi.org/10.15252/emmm.202115098Alzheimer’s diseasebiomarkersCSFp‐tau235tau |
| spellingShingle | Juan Lantero‐Rodriguez Anniina Snellman Andrea L Benedet Marta Milà‐Alomà Elena Camporesi Laia Montoliu‐Gaya Nicholas J Ashton Agathe Vrillon Thomas K Karikari Juan Domingo Gispert Gemma Salvadó Mahnaz Shekari Christina E Toomey Tammaryn L Lashley Henrik Zetterberg Marc Suárez‐Calvet Gunnar Brinkmalm Pedro Rosa Neto Kaj Blennow P‐tau235: a novel biomarker for staging preclinical Alzheimer’s disease EMBO Molecular Medicine Alzheimer’s disease biomarkers CSF p‐tau235 tau |
| title | P‐tau235: a novel biomarker for staging preclinical Alzheimer’s disease |
| title_full | P‐tau235: a novel biomarker for staging preclinical Alzheimer’s disease |
| title_fullStr | P‐tau235: a novel biomarker for staging preclinical Alzheimer’s disease |
| title_full_unstemmed | P‐tau235: a novel biomarker for staging preclinical Alzheimer’s disease |
| title_short | P‐tau235: a novel biomarker for staging preclinical Alzheimer’s disease |
| title_sort | p tau235 a novel biomarker for staging preclinical alzheimer s disease |
| topic | Alzheimer’s disease biomarkers CSF p‐tau235 tau |
| url | https://doi.org/10.15252/emmm.202115098 |
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