Biomarkers for tau pathology

https://doi.org/10.1016/j.mcn.2018.12.001Get rights and content
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Highlights

  • Biomarkers for tau pathology are now essential to the research framework in the diagnosis of Alzheimer's disease (AD)

  • Measurement of t- and p-tau has been possible in cerebrospinal fluid (CSF) for some time, the recent development of positron emission tomography (PET) ligands binding to tau has added the possibility to map and quantify tau in the living brain

  • First-generation tau PET ligands bind predominantly to AD-typical 3R/4R tau isoforms and exhibit off-target binding that can limit accurate ligand uptake quantification

  • Second-generation tau PET ligands appear to bind to comparable binding sites but exhibit fewer issues with brain off-target binding

  • Biomarkers for tau derived from CSF analysis and PET could provide complementary information about disease state and stage

  • At this time, T-tau, but not p-tau, can be reliably measured in plasma using ultra-sensitive immunoassays.

Abstract

The aggregation of fibrils of hyperphosphorylated and C-terminally truncated microtubule-associated tau protein characterizes 80% of all dementia disorders, the most common neurodegenerative disorders. These so-called tauopathies are hitherto not curable and their diagnosis, especially at early disease stages, has traditionally proven difficult. A keystone in the diagnosis of tauopathies was the development of methods to assess levels of tau protein in vivo in cerebrospinal fluid, which has significantly improved our knowledge about these conditions. Tau proteins have also been measured in blood, but the importance of tau-related changes in blood is still unclear. The recent addition of positron emission tomography ligands to visualize, map and quantify tau pathology has further contributed with information about the temporal and spatial characteristics of tau accumulation in the living brain. Together, the measurement of tau with fluid biomarkers and positron emission tomography constitutes the basis for a highly active field of research.

This review describes the current state of biomarkers for tau biomarkers derived from neuroimaging and from the analysis of bodily fluids and their roles in the detection, diagnosis and prognosis of tau-associated neurodegenerative disorders, as well as their associations with neuropathological findings, and aims to provide a perspective on how these biomarkers might be employed prospectively in research and clinical settings.

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These authors have contributed equally.