Associations of Plasma Phospho-Tau217 Levels With Tau Positron Emission Tomography in Early Alzheimer Disease.
Associations of Plasma Phospho-Tau217 Levels With Tau Positron Emission Tomography in Early Alzheimer Disease.
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早期阿尔茨海默病患者血浆磷酸化Tau 217水平与Tau正电子发射断层扫描的相关性
DOI：
10.1001/jamaneurol.2020.4201
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发表时间：
2021-02-01
期刊：
影响因子：
29
通讯作者：
Hansson O
中科院分区：
文献类型：
--
作者：
Janelidze S;Berron D;Smith R;Strandberg O;Proctor NK;Dage JL;Stomrud E;Palmqvist S;Mattsson-Carlgren N;Hansson O
这项队列研究比较了血浆中苏氨酸217磷酸化tau蛋白水平与早期阿尔茨海默病中已建立的脑脊液和正电子发射断层扫描（PET）tau蛋白生物标志物。在阿尔茨海默病的病程中，与已建立的脑脊液和正电子发射断层扫描（PET）tau生物标志物的水平相比，血浆中苏氨酸217磷酸化的tau（P-tau 217）水平在多早开始变化？在这项对490名无痴呆症个体的队列研究中，淀粉样蛋白-β阳性认知未受损参与者的血浆P-tau 217水平在不溶性tau聚集体通过tau-PET检测到之前升高;建模方法预测，血浆和脑脊液P-tau 217在内嗅皮质中的tau-PET之前增加，随后是更广泛的皮质tau-PET变化。研究结果表明，在阿尔茨海默病中，血浆P-tau 217在tau-PET之前变得异常，并且血浆P-tau 217可以被认为是早期阿尔茨海默病的生物标志物。目前迫切需要廉价且微创的阿尔茨海默病（AD）血液生物标志物，可用于检测早期疾病变化。为了评估与AD病理学的已建立的脑脊液（CSF）和正电子发射断层扫描（PET）生物标志物水平相比，在AD过程中，在苏氨酸217（P-tau 217）磷酸化的tau血浆水平有多早开始变化。这项队列研究包括认知健康的对照个体（n = 225）和来自BioFINDER-2研究的主观认知下降（n = 89）或轻度认知障碍（n = 176）的参与者。参与者于2017年1月至2019年10月在瑞典的2家不同医院入组。所有研究参与者均接受了血浆P-tau 217评估以及tau和淀粉样蛋白-β（Aβ）-PET成像。111名参与者的子队列进行了2或3次tau-PET扫描。临床前和前驱AD患者血浆P-tau 217水平的变化与CSF P-tau 217和PET测量值的变化的比较在490名参与者中，251名为女性（51.2%），平均（SD）年龄为65.9（13.1）岁。在Aβ-PET异常但内嗅皮质中tau-PET正常的认知未受损受试者中，血浆P-tau 217水平升高（Aβ-PET+/ tau-PET-组vs Aβ-PET-/ tau-PET-组：中位数，2.2 pg/mL [四分位距（IQR），1.5-2.9 pg/mL] vs 0.7 pg/mL [IQR，0.3-1.4 pg/mL]）。大多数血浆P-tau 217和tau-PET不一致的认知未受损受试者血浆P-tau 217阳性，tau-PET阴性（P-tau 217 +/tau-PET-：36 [94.7%]; P-tau 217-/tau-PET+：2 [5.3%]）。横断面数据的基于事件的建模预测，在认知未受损的参与者和轻度认知障碍的参与者中，血浆和CSF P-tau 217都将在内嗅皮质中的tau-PET信号之前发生变化，随后是更广泛的皮质tau-PET变化。当在非线性样条模型中检验与总体Aβ负荷的相关性时，与tau-PET测量值相比，在较低的Aβ-PET值下，血浆和CSF P-tau 217均升高。在基线tau-PET正常的受试者中，基线血浆P-tau 217异常的受试者的内嗅皮质中tau-PET纵向增加率更高（中位标准化摄取值比值，0.029 [IQR，-0.006至0.041] vs -0.001 [IQR，-0.021至0.020]; Mann-Whitney U，P = 0.02）。在该队列研究中，在AD的早期临床前阶段期间，血浆P-tau 217水平增加，此时tau-PET尚未检测到不溶性tau聚集体。血浆P-tau 217可能有望作为早期AD脑病理学的生物标志物。
This cohort study compares plasma levels of phosphorylated tau at threonine 217 with established cerebrospinal fluid and positron emission tomography (PET) tau biomarkers in early Alzheimer disease. How early in the course of Alzheimer disease do plasma levels of tau phosphorylated at threonine 217 (P-tau217) start to change compared with levels of established cerebrospinal fluid and positron emission tomography (PET) tau biomarkers? In this cohort study of 490 individuals without dementia, plasma P-tau217 levels were elevated in amyloid-β–positive cognitively unimpaired participants before insoluble tau aggregates became detectable by tau-PET; modeling approaches predicted that both plasma and cerebrospinal fluid P-tau217 increased before tau-PET in the entorhinal cortex followed by more widespread cortical tau-PET changes. The study results suggest that in Alzheimer disease, plasma P-tau217 becomes abnormal before tau-PET and that plasma P-tau217 may be considered as an early Alzheimer disease biomarker. There is an urgent need for inexpensive and minimally invasive blood biomarkers for Alzheimer disease (AD) that could be used to detect early disease changes. To 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. This 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. Changes in plasma P-tau217 levels in preclinical and prodromal AD compared with changes in CSF P-tau217 and PET measures. Of 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). In 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.
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影响因子：
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作者：
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通讯作者：
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