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Assessment Of Plasma Total Tau Level As A Predictive Biomarker For Dementia And Related Endophenotypes

Matthew P Pase, Alexa Beiser, Jayandra J Himali, Claudia L. Satizabal, Hugo J. Aparicio, Charles DeCarli, Geneviève Chêne, Carole Dufouil, Sudha Seshadri
Published 2019 · Medicine
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Importance Blood-based biomarkers have the potential to improve the identification of persons with the greatest dementia risk for inclusion in dementia prevention trials through low-cost and minimally invasive screening. Objective To investigate the use of plasma total tau as a blood biomarker for dementia and related endophenotypes. Design, Setting, and Participants This prospective cohort study used data from the US community-based Framingham Heart Study with replication in the Memento study, a multicenter cohort of persons with mild cognitive impairment or subjective cognitive complaints recruited from memory clinics across France. Total tau levels were measured from stored plasma samples in Framingham Heart Study participants during 2004 to 2011. Dementia follow-up occurred across a median of 6 years (interquartile range, 5-8 years) for persons 65 years and older who were dementia free at baseline. Plasma and/or cerebrospinal fluid samples were obtained from Memento study participants from April 19, 2011, to June 22, 2016. Dementia follow-up took place over a median of 4 years (interquartile range, 3-5 years). Data analysis was performed from January to November 2018. Exposures Plasma total tau level measured using single-molecule array technology. Main Outcomes and Measures Incidence of dementia of any cause (all dementia) and dementia due to clinical Alzheimer disease (AD dementia). Results Among the 1453 participants in the Framingham dementia study sample, the mean (SD) age was 75 (7) years; 792 (54.5%) were female. Among the 367 individuals in the replication cohort, the mean (SD) age was 69 (9) years; 217 (59.1%) were female. Of 134 cases of incident all dementia in the Framingham sample, 105 were AD dementia. After adjustment for age and sex, each SD unit increase in the log of plasma total tau level was associated with a 35% increase in AD dementia risk (hazard ratio [HR], 1.35; 95% CI, 1.10-1.67). The addition of plasma total tau to a model including age and sex improved the stratification of participants for risk of AD dementia (net reclassification improvement, 0.382; 95% CI, 0.030-0.716). Higher plasma total tau level was associated with poorer cognition across 7 cognitive tasks (P < .05) and smaller hippocampi (hippocampal volume: &bgr; [SE] = 0.002 [0.001]; P = .003) as well as neurofibrillary tangles (&bgr; [SE] = 0.95 [0.45]; P = .04) and microinfarcts (odds ratio, 3.04; 95% CI, 1.26-7.37) at autopsy. In the replication cohort, plasma total tau level weakly correlated with cerebrospinal fluid total tau level (Spearman correlation coefficient, 0.16; P = .07), but plasma total tau was at least as strongly associated with incident AD dementia as cerebrospinal fluid total tau (log plasma total tau: HR, 2.33; 95% CI, 1.00-5.48; log cerebrospinal fluid total tau: HR, 2.14; 95% CI, 1.33-3.44) after adjustment for age and sex. Conclusions and Relevance The findings suggest that plasma total tau levels may improve the prediction of future dementia, are associated with dementia endophenotypes, and may be used as a biomarker for risk stratification in dementia prevention trials.
This paper references
The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease
André Delacourte (1999)
Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study
David L. Bachman (1992)
The A4 Study: Stopping AD Before Symptoms Begin?
Reisa A. Sperling (2014)
Epidemiological approaches to heart disease: the Framingham Study.
Thomas R. Dawber (1951)
The Third Generation Cohort of the National Heart, Lung, and Blood Institute's Framingham Heart Study: design, recruitment, and initial examination.
Greta Lee Splansky (2007)
Simultaneous detection of single molecules and singulated ensembles of molecules enables immunoassays with broad dynamic range.
David Michael Rissin (2011)
APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts
Jing Qian (2017)
Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort
Carole Dufouil (2017)
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease
Jean-Charles Lambert (2013)
Incidence of Dementia over Three Decades in the Framingham Heart Study.
Claudia L. Satizabal (2016)
Role of Improved Vascular Health in the Declining Incidence of Dementia
Matthew P Pase (2017)
Measures of brain morphology and infarction in the framingham heart study: establishing what is normal
Charles DeCarli (2005)
Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer's Disease.
Kacie D. Deters (2017)
Levels of tau protein in plasma are associated with neurodegeneration and cognitive function in a population-based elderly cohort
Jeffrey L. Dage (2016)
Trail Making Test A and B: normative data stratified by age and education.
Tom N. Tombaugh (2004)
Defining MCI in the Framingham Heart Study Offspring: education versus WRAT-based norms.
Richard E. Ahl (2013)
Anatomical mapping of white matter hyperintensities (WMH): exploring the relationships between periventricular WMH, deep WMH, and total WMH burden.
Charles DeCarli (2005)
Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
Reisa A. Sperling (2011)
Plasma tau in Alzheimer disease
Niklas Mattsson (2016)
Multi-atlas based segmentation of brain images: Atlas selection and its effect on accuracy
Paul Aljabar (2009)
A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary
Otfried Spreen (1991)
The Framingham Brain Donation Program: neuropathology along the cognitive continuum.
Rhoda Au (2012)
Adaptive image segmentation for robust measurement of longitudinal brain tissue change
Evan Fletcher (2012)
Association of Plasma Total Tau Level With Cognitive Decline and Risk of Mild Cognitive Impairment or Dementia in the Mayo Clinic Study on Aging
Michelle M. Mielke (2017)
Plasma tau levels in Alzheimer's disease
Henrik Zetterberg (2013)
Tau proteins in serum predict neurological outcome after hypoxic brain injury from cardiac arrest: results of a pilot study.
Jeffrey D. Randall (2013)
Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers.
Michael J Pencina (2011)
Diagnostic and Statistical Manual of Mental Disorders
Janet B. W. Williams (2013)
Tau plasma levels in subjective cognitive decline: Results from the DELCODE study
Stephan Müller (2017)
MRI non-uniformity correction through interleaved bias estimation and B-spline deformation with a template
Evan Fletcher (2012)
Tau as a biomarker of neurodegenerative diseases.
Susanna Schraen-Maschke (2008)
NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease
Clifford R. Jack (2018)
"Mini-mental state". A practical method for grading the cognitive state of patients for the clinician.
Marshal F. Folstein (1975)
Clinical diagnosis of Alzheimer's disease
Guy Mckhann (1984)
The Framingham Offspring Study. Design and preliminary data.
Manning Feinleib (1975)
Confidence interval estimates of an index of quality performance based on logistic regression models.
David W. Hosmer (1995)
Neuropathological stageing of Alzheimer-related changes
Heiko Braak (1991)
Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond.
Michael J Pencina (2008)
CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis
Bob Olsson (2016)
Single-Molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations
David Michael Rissin (2010)

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Morvane Colin (2019)
Occupational metals exposure and cognitive performance among foundry workers using tau protein as a biomarker.
Rateba S Mohammed (2019)
Association of CD14 with incident dementia and markers of brain aging and injury
Matthew P Pase (2020)
An update on fluid biomarkers for neurodegenerative diseases: recent success and challenges ahead
Joel Simrén (2020)
Plasma tau, neurofilament light chain and amyloid-β levels and risk of dementia; a population-based cohort study
Frank de Wolf (2020)
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