Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility

Recent technological advances have enabled the detection of specific forms of phosphorylated tau in blood. Here, the authors summarize the performance of blood phosphorylated tau biomarkers in the context of Alzheimer disease and highlight related ethical, analytical and clinical challenges. Well-authenticated biomarkers can provide critical insights into the biological basis of Alzheimer disease (AD) to enable timely and accurate diagnosis, estimate future burden and support therapeutic trials. Current cerebrospinal fluid and molecular neuroimaging biomarkers fulfil these criteria but lack the scalability and simplicity necessary for widespread application. Blood biomarkers of adequate effectiveness have the potential to act as first-line diagnostic and prognostic tools, and offer the possibility of extensive population screening and use that is not limited to specialized centres. Accelerated progress in our understanding of the biochemistry of brain-derived tau protein and advances in ultrasensitive technologies have enabled the development of AD-specific phosphorylated tau (p-tau) biomarkers in blood. In this Review we discuss how new information on the molecular processing of brain p-tau and secretion of specific fragments into biofluids is informing blood biomarker development, enabling the evaluation of preanalytical factors that affect quantification, and informing harmonized protocols for blood handling. We also review the performance of blood p-tau biomarkers in the context of AD and discuss their potential contexts of use for clinical and research purposes. Finally, we highlight outstanding ethical, clinical and analytical challenges, and outline the steps that need to be taken to standardize inter-laboratory and inter-assay measurements.

Automated summary

This article summarizes the performance of blood phosphorylated tau biomarkers in the context of Alzheimer disease (AD) and discusses the related ethical, analytical, and clinical challenges. It highlights the potential of blood biomarkers as first-line diagnostic and prognostic tools, but emphasizes the need to address outstanding ethical, clinical, and analytical challenges, and standardize inter-laboratory and inter-assay measurements.