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Plasma P‐tau immunoassays, methodological aspects and clinical performance
Author(s) -
Blennow Kaj
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.037515
Subject(s) - neurodegeneration , biomarker , medicine , dementia , concordance , pathology , amyloid (mycology) , alzheimer's disease , disease , cerebrospinal fluid , oncology , chemistry , biochemistry
Background The promise of novel disease‐modifying therapies for Alzheimer’s disease (AD) calls for simple and widely available screening tests for AD‐type pathophysiology, specifically brain amyloidosis (A), tau pathology (T) and neurodegeneration (N). Technical developments have given analytical tools to measure AD protein biomarkers in blood samples. The plasma Aβ42/40 ratio shows high concordance with amyloid PET and blood neurofilament light (NFL) is a sensitive marker for neurodegeneration. CSF P‐tau181 is a well‐established and disease‐specific AD biomarker, but in addition, blood biomarkers for brain tau pathology is urgently needed. Method Immunoassays with analytical sensitivity in the low pg/mL range has been developed for P‐tau181 in both plasma and serum samples, with blood levels correlating tightly with corresponding CSF levels in paired samples. Immunoprecipitation mass spectrometry (IP‐MS) experiments verify that the P‐tau181 Simoa assay specifically measure tau phosphorylated at Threonine 181. Result Results from several clinical cohorts show that P‐tau181 is markedly increased along the whole AD continuum, from Aβ‐positive cognitively unimpaired elderly to AD dementia cases (p<0.0001). Plasma p‐tau181 also distinguishes AD from other tauopathies and neurodegenerative disorders, e.g. FTD, PSP/CBD, PD and vascular dementia, with AUC values of 83‐100%. Importantly, plasma p‐tau181 is associated with tau (MK‐6240) PET positivity (AUC>90%), but is also increased in the very early phase of AD, in amyloid PET positive but tau PET negative (Braak stage 0) individuals. Conclusion Plasma p‐tau181 is a novel promising blood biomarker for AD‐type tau pathophysiology. Blood p‐tau181 may be developed into a simple, cost‐effective and scalable test for screening and diagnosis of AD.