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Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography.

ABSTRACT: INTRODUCTION:We examined and compared plasma phospho-tau181 (pTau181) and total tau: (1) across the Alzheimer's disease (AD) clinical spectrum; (2) in relation to brain amyloid ? (A?) positron emission tomography (PET), tau PET, and cortical thickness; and (3) as a screening tool for elevated brain A?. METHODS:Participants included 172 cognitively unimpaired, 57 mild cognitively impaired, and 40 AD dementia patients with concurrent A? PET (Pittsburgh compound B), tau PET (AV1451), magnetic resonance imaging, plasma total tau, and pTau181. RESULTS:Plasma total tau and pTau181 levels were higher in AD dementia patients than those in cognitively unimpaired. Plasma pTau181 was more strongly associated with both A? and tau PET. Plasma pTau181 was a more sensitive and specific predictor of elevated brain A? than total tau and was as good as, or better than, the combination of age and apolipoprotein E (APOE). DISCUSSION:Plasma pTau181 may have utility as a biomarker of AD pathophysiology and as a noninvasive screener for elevated brain A?.

SUBMITTER: Mielke MM

PROVIDER: S-EPMC6097897 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography.

Mielke Michelle M MM Hagen Clinton E CE Xu Jing J Chai Xiyun X Vemuri Prashanthi P Lowe Val J VJ Airey David C DC Knopman David S DS Roberts Rosebud O RO Machulda Mary M MM Jack Clifford R CR Petersen Ronald C RC Dage Jeffrey L JL

Alzheimer's & dementia : the journal of the Alzheimer's Association 20180405 8

<h4>Introduction</h4>We examined and compared plasma phospho-tau181 (pTau181) and total tau: (1) across the Alzheimer's disease (AD) clinical spectrum; (2) in relation to brain amyloid β (Aβ) positron emission tomography (PET), tau PET, and cortical thickness; and (3) as a screening tool for elevated brain Aβ.<h4>Methods</h4>Participants included 172 cognitively unimpaired, 57 mild cognitively impaired, and 40 AD dementia patients with concurrent Aβ PET (Pittsburgh compound B), tau PET (AV1451), ...[more]

PMID: 29626426

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Project description:ImportanceThere is an urgent need for inexpensive and minimally invasive blood biomarkers for Alzheimer disease (AD) that could be used to detect early disease changes.ObjectiveTo assess how early in the course of AD plasma levels of tau phosphorylated at threonine 217 (P-tau217) start to change compared with levels of established cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers of AD pathology.Design, setting, and participantsThis cohort study included cognitively healthy control individuals (n = 225) and participants with subjective cognitive decline (n = 89) or mild cognitive impairment (n = 176) from the BioFINDER-2 study. Participants were enrolled at 2 different hospitals in Sweden from January 2017 to October 2019. All study participants underwent plasma P-tau217 assessments and tau- and amyloid-β (Aβ)-PET imaging. A subcohort of 111 participants had 2 or 3 tau-PET scans.Main outcomes and measuresChanges in plasma P-tau217 levels in preclinical and prodromal AD compared with changes in CSF P-tau217 and PET measures.ResultsOf 490 participants, 251 were women (51.2%) and the mean (SD) age was 65.9 (13.1) years. Plasma P-tau217 levels were increased in cognitively unimpaired participants with abnormal Aβ-PET but normal tau-PET in the entorhinal cortex (Aβ-PET+/ tau-PET- group vs Aβ-PET-/ tau-PET- group: median, 2.2 pg/mL [interquartile range (IQR), 1.5-2.9 pg/mL] vs 0.7 pg/mL [IQR, 0.3-1.4 pg/mL]). Most cognitively unimpaired participants who were discordant for plasma P-tau217 and tau-PET were positive for plasma P-tau217 and negative for tau-PET (P-tau217+/tau-PET-: 36 [94.7%]; P-tau217-/tau-PET+: 2 [5.3%]). Event-based modeling of cross-sectional data predicted that in cognitively unimpaired participants and in those with mild cognitive impairment, both plasma and CSF P-tau217 would change before the tau-PET signal in the entorhinal cortex, followed by more widespread cortical tau-PET changes. When testing the association with global Aβ load in nonlinear spline models, both plasma and CSF P-tau217 were increased at lower Aβ-PET values compared with tau-PET measures. Among participants with normal baseline tau-PET, the rates of longitudinal increase in tau-PET in the entorhinal cortex were higher in those with abnormal plasma P-tau217 at baseline (median standardized uptake value ratio, 0.029 [IQR, -0.006 to 0.041] vs -0.001 [IQR, -0.021 to 0.020]; Mann-Whitney U, P = .02).Conclusions and relevanceIn this cohort study, plasma P-tau217 levels were increased during the early preclinical stages of AD when insoluble tau aggregates were not yet detectable by tau-PET. Plasma P-tau217 may hold promise as a biomarker for early AD brain pathology.

Dataset Information

Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography.

Publications

Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography.

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