Total and phosphorylated tau protein as biological markers of Alzheimer's disease.

Hdl Handle:
http://hdl.handle.net/10147/207861
Title:
Total and phosphorylated tau protein as biological markers of Alzheimer's disease.
Authors:
Hampel, Harald; Blennow, Kaj; Shaw, Leslie M; Hoessler, Yvonne C; Zetterberg, Henrik; Trojanowski, John Q
Affiliation:
Discipline of Psychiatry, School of Medicine & Trinity College Institute of, Neuroscience, Laboratory of Neuroimaging & Biomarker Research, Trinity College,, University of Dublin, The Adelaide and Meath Hospital Incorporating The National , Children's Hospital, Tallaght, Dublin, Ireland. harald.hampel@med.uni-muenchen.de
Citation:
Exp Gerontol. 2010 Jan;45(1):30-40. Epub 2009 Oct 22.
Journal:
Experimental gerontology
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207861
DOI:
10.1016/j.exger.2009.10.010
PubMed ID:
19853650
Abstract:
Advances in our understanding of tau-mediated neurodegeneration in Alzheimer's disease (AD) are moving this disease pathway to center stage for the development of biomarkers and disease modifying drug discovery efforts. Immunoassays were developed detecting total (t-tau) and tau phosphorylated at specific epitopes (p-tauX) in cerebrospinal fluid (CSF), methods to analyse tau in blood are at the experimental beginning. Clinical research consistently demonstrated CSF t- and p-tau increased in AD compared to controls. Measuring these tau species proved informative for classifying AD from relevant differential diagnoses. Tau phosphorylated at threonine 231 (p-tau231) differentiated between AD and frontotemporal dementia, tau phosphorylated at serine 181 (p-tau181) enhanced classification between AD and dementia with Lewy bodies. T- and p-tau are considered "core" AD biomarkers that have been successfully validated by controlled large-scale multi-center studies. Tau biomarkers are implemented in clinical trials to reflect biological activity, mechanisms of action of compounds, support enrichment of target populations, provide endpoints for proof-of-concept and confirmatory trials on disease modification. World-wide quality control initiatives are underway to set required methodological and protocol standards. Discussions with regulatory authorities gain momentum defining the role of tau biomarkers for trial designs and how they may be further qualified for surrogate marker status.
Language:
eng
MeSH:
Aged; Alzheimer Disease/*diagnosis/*metabolism; Biological Markers/blood/*cerebrospinal fluid; Humans; Nerve Degeneration/diagnosis/metabolism; Phosphorylation; Predictive Value of Tests; tau Proteins/*metabolism
ISSN:
1873-6815 (Electronic); 0531-5565 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorHampel, Haralden_GB
dc.contributor.authorBlennow, Kajen_GB
dc.contributor.authorShaw, Leslie Men_GB
dc.contributor.authorHoessler, Yvonne Cen_GB
dc.contributor.authorZetterberg, Henriken_GB
dc.contributor.authorTrojanowski, John Qen_GB
dc.date.accessioned2012-02-01T10:48:22Z-
dc.date.available2012-02-01T10:48:22Z-
dc.date.issued2012-02-01T10:48:22Z-
dc.identifier.citationExp Gerontol. 2010 Jan;45(1):30-40. Epub 2009 Oct 22.en_GB
dc.identifier.issn1873-6815 (Electronic)en_GB
dc.identifier.issn0531-5565 (Linking)en_GB
dc.identifier.pmid19853650en_GB
dc.identifier.doi10.1016/j.exger.2009.10.010en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207861-
dc.description.abstractAdvances in our understanding of tau-mediated neurodegeneration in Alzheimer's disease (AD) are moving this disease pathway to center stage for the development of biomarkers and disease modifying drug discovery efforts. Immunoassays were developed detecting total (t-tau) and tau phosphorylated at specific epitopes (p-tauX) in cerebrospinal fluid (CSF), methods to analyse tau in blood are at the experimental beginning. Clinical research consistently demonstrated CSF t- and p-tau increased in AD compared to controls. Measuring these tau species proved informative for classifying AD from relevant differential diagnoses. Tau phosphorylated at threonine 231 (p-tau231) differentiated between AD and frontotemporal dementia, tau phosphorylated at serine 181 (p-tau181) enhanced classification between AD and dementia with Lewy bodies. T- and p-tau are considered "core" AD biomarkers that have been successfully validated by controlled large-scale multi-center studies. Tau biomarkers are implemented in clinical trials to reflect biological activity, mechanisms of action of compounds, support enrichment of target populations, provide endpoints for proof-of-concept and confirmatory trials on disease modification. World-wide quality control initiatives are underway to set required methodological and protocol standards. Discussions with regulatory authorities gain momentum defining the role of tau biomarkers for trial designs and how they may be further qualified for surrogate marker status.en_GB
dc.language.isoengen_GB
dc.subject.meshAgeden_GB
dc.subject.meshAlzheimer Disease/*diagnosis/*metabolismen_GB
dc.subject.meshBiological Markers/blood/*cerebrospinal fluiden_GB
dc.subject.meshHumansen_GB
dc.subject.meshNerve Degeneration/diagnosis/metabolismen_GB
dc.subject.meshPhosphorylationen_GB
dc.subject.meshPredictive Value of Testsen_GB
dc.subject.meshtau Proteins/*metabolismen_GB
dc.titleTotal and phosphorylated tau protein as biological markers of Alzheimer's disease.en_GB
dc.contributor.departmentDiscipline of Psychiatry, School of Medicine & Trinity College Institute of, Neuroscience, Laboratory of Neuroimaging & Biomarker Research, Trinity College,, University of Dublin, The Adelaide and Meath Hospital Incorporating The National , Children's Hospital, Tallaght, Dublin, Ireland. harald.hampel@med.uni-muenchen.deen_GB
dc.identifier.journalExperimental gerontologyen_GB
dc.description.provinceLeinster-

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