Quantification of tau peptides in blood samples using a new mass spectrometry method suggests that individual phosphorylated tau peptides have distinct patterns of emergence in Alzheimer’s disease and differential associations with amyloid and tau pathologies. This method has the potential to stage patients along the disease continuum and for clinical trials.
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Ossenkoppele, R. et al. Tau biomarkers in Alzheimer’s disease: towards implementation in clinical practice and trials. Lancet Neurol. 21, 726–734 (2022). This review describes the basics of tau pathology in AD and provides an update on tau biomarkers (PET, cerebrospinal fluid and plasma).
van Dyck, C. H. et al. Lecanemab in early Alzheimer’s disease. N. Engl. J. Med. 388, 9–21 (2023). This paper reports the results from the successful phase 3 clinical trial of a monoclonal antibody that binds with high affinity to Aβ soluble protofibrils.
Ashton, N. J. et al. Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring. Nat. Med. 28, 2555–2562 (2022). This paper highlights p-tau217 as a surrogate marker of disease progression in preclinical and prodromal AD.
Karikari, T. K. et al. Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility. Nat. Rev. Neurol. 18, 400–418 (2022). This review summarizes the performance and potential use of blood p-tau biomarkers in AD.
Gobom, J. et al. Antibody-free measurement of cerebrospinal fluid tau phosphorylation across the Alzheimer’s disease continuum. Mol. Neurodegener. 17, 81 (2022). This paper reports the MS method to quantify several tau peptides that was the precursor of the approach used in the current study.
Pontecorvo, M. J. et al. Association of donanemab treatment with exploratory plasma biomarkers in early symptomatic Alzheimer disease: a secondary analysis of the TRAILBLAZER-ALZ randomized clinical trial. JAMA Neurol. 79, 1250–1259 (2022). This paper reports the results from a clinical trial in which participants were selected on the basis of intermediate tau PET burden.
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This is a summary of: Montoliu-Gaya, L. et al. Mass spectrometric simultaneous quantification of tau species in plasma shows differential associations with amyloid and tau pathologies. Nat. Aging, https://doi.org/10.1038/s43587-023-00405-1 (2023).
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New mass spectrometry method to simultaneously quantify several tau species in blood. Nat Aging 3, 638–639 (2023). https://doi.org/10.1038/s43587-023-00434-w