Two novel blood-based biomarker candidates measuring degradation of tau are associated with dementia: A prospective study

Jesper Skov Neergaard,Katrine Dragsbæk,Morten Asser Karsdal,Claus Christiansen,Kim Henriksen,Susanne Brix,Stephen D Ginsberg

doi:10.1371/journal.pone.0194802

Jesper Skov Neergaard, Katrine Dragsbæk + Show 5 more

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https://doi.org/10.1371/journal.pone.0194802

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Abstract

BackgroundTruncated tau appears to be specifically related to disease pathology and recent studies have shown the presence and elevation of several truncated tau species in Cerebrospinal fluid (CSF) of subjects with Alzheimer’s disease (AD); however, the relevance of truncated Tau measurements in blood is still being studied.ObjectiveThe aim of the current study was to assess the longitudinal associations between baseline levels of two novel blood biomarker candidates measuring truncated tau, Tau-A and Tau-C, and the risk of incident dementia and AD in elderly women.MethodsUsing solid phase competitive ELISA, two tau fragments were detected in serum of 5,309 women from the Prospective Epidemiological Risk Factor study. The study was an observational, prospective study of Danish postmenopausal women. Subjects were followed with registry-linkage for up to 15 years (median follow-up time 13.7 years). Cox regression was used to assess the utility of the biomarker candidates in relation to dementia and AD.ResultsHigh levels of Tau-A and Tau-C (above the median) in blood were associated with lower risk of dementia and AD (Tau-A: Dementia HR[95% CI] = 0.85[0.70–1.04]; AD 0.71[0.52–0.98] and Tau-C: Dementia 0.84[0.70–1.00]; AD 0.78[0.60–1.03]). Tau-C gave a very modest increase in the AUC in a 5-year prediction horizon as compared to a reference model with age and education, while a combination of the two did not improve their predictive capacity.ConclusionsMeasurement of tau in serum is feasible. The serological tau turnover profile may be related to the diagnosis and development of dementia and AD. The exact processing and profile in serum in relation to cognitive disorders remains to be further assessed to provide simple non-invasive tests to identify subjects with progressive cognitive disorders.

Highlights

The global burden of dementia is rising, with a new case registered every 3.2 seconds
Truncated tau appears to be related to disease pathology and recent studies have shown the presence and elevation of several truncated tau species in Cerebrospinal fluid (CSF) of subjects with Alzheimer’s disease (AD); the relevance of truncated Tau measurements in blood is still being studied
Cox regression was used to assess the utility of the biomarker candidates in relation to dementia and AD

Summary

Introduction

The global burden of dementia is rising, with a new case registered every 3.2 seconds. Dementia is ranked as the 9th most burdensome disease for people aged 60 years and older, the costs associated with dementia are enormous and place dementia as the most expensive disease in the United States The reason for this increase in dementia prevalence and the following increased costs are mainly caused by the shifting epidemiological trend of increasing numbers of elder people, caused by low fertility rates and increasing longevity [1,2]. To counteract this dreary trend there is a need for better treatments. Truncated tau appears to be related to disease pathology and recent studies have shown the presence and elevation of several truncated tau species in Cerebrospinal fluid (CSF) of subjects with Alzheimer’s disease (AD); the relevance of truncated Tau measurements in blood is still being studied

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Conclusion