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血浆磷酸化-tau蛋白217可准确鉴别阿尔茨海默病
2020-07-29 22:44

瑞典斯科讷大学医院Oskar Hansson团队分析了血浆磷酸化-tau蛋白217鉴别阿尔茨海默病和其他神经退行性疾病的准确性。2020年7月28日,该研究发表在《美国医学会杂志》上。

目前阿尔茨海默病(AD)的诊断检测方法存在局限性。为了检验血浆中217号苏氨酸磷酸化的tau蛋白(P-tau217)作为生物标志物诊断AD的准确性,研究组进行了一项横断面研究。

2007年5月至2019年1月,研究组在美国亚利桑那州招募了34名AD患者和47名非AD参与者(队列1);2017年4月至2019年9月,在瑞典招募了301例无认知障碍的参与者,178例轻度认知障碍(MCI)者,121例AD痴呆患者,99例其他神经退行性疾病患者(队列2);2013年12月至2017年2月,在哥伦比亚招募了364例PSEN1 E280A突变携带者和257例突变非携带者(队列3)。

队列1的平均年龄为83.5岁,队列2为69.1岁,队列3为35.8岁。队列1中女性占38%,队列2为51%,队列3为57%。队列1中血浆P-tau217可将神经病理学定义的AD与非AD区别开,曲线下面积(AUC)为0.89,准确性明显高于血浆P-tau181和神经丝轻链(NfL)。

队列2中血浆P-tau217对临床AD痴呆与其他神经退行性疾病的诊断准确性(AUC为0.96)显著高于血浆P-tau181、血浆NfL和MRI测量值,但与脑脊液(CSF)P-tau217、CSF P-tau181和tau-PET相比没有显著差异。队列3中,从大约25岁及以上开始,PSEN1突变携带者中的血浆P-tau217水平显著高于非携带者,比携带者预计的MCI发病时间早了20年。

队列1中,参与者血浆P-tau217水平与tau蛋白缠结相关,但与β-淀粉样斑块无关。队列2中,血浆P-tau217可区分异常与正常tau-PET扫描(AUC为0.93),其准确度明显高于血浆P-tau181、血浆NfL、CSF P-tau181、CSF Aβ42 :Aβ40比值和MRI测量值,但与CSF P-tau217相比无显著差异。

总之,血浆P-tau217可将AD与其他神经退行性疾病区别开来,其准确度明显高于基于血浆和MRI的生物标志物,但与基于CSF或PET的关键指标相比并无显著差异。

附:英文原文

Title: Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders

Author: Sebastian Palmqvist, Shorena Janelidze, Yakeel T. Quiroz, Henrik Zetterberg, Francisco Lopera, Erik Stomrud, Yi Su, Yinghua Chen, Geidy E. Serrano, Antoine Leuzy, Niklas Mattsson-Carlgren, Olof Strandberg, Ruben Smith, Andres Villegas, Diego Sepulveda-Falla, Xiyun Chai, Nicholas K. Proctor, Thomas G. Beach, Kaj Blennow, Jeffrey L. Dage, Eric M. Reiman, Oskar Hansson

Issue&Volume: 2020-07-28

Abstract: Importance  There are limitations in current diagnostic testing approaches for Alzheimer disease (AD).

Objective  To examine plasma tau phosphorylated at threonine 217 (P-tau217) as a diagnostic biomarker for AD.

Design, Setting, and Participants  Three cross-sectional cohorts: an Arizona-based neuropathology cohort (cohort 1), including 34 participants with AD and 47 without AD (dates of enrollment, May 2007-January 2019); the Swedish BioFINDER-2 cohort (cohort 2), including cognitively unimpaired participants (n=301) and clinically diagnosed patients with mild cognitive impairment (MCI) (n=178), AD dementia (n=121), and other neurodegenerative diseases (n=99) (April 2017-September 2019); and a Colombian autosomal-dominant AD kindred (cohort 3), including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers (December 2013-February 2017).

Exposures  Plasma P-tau217.

Main Outcomes and Measures  Primary outcome was the discriminative accuracy of plasma P-tau217 for AD (clinical or neuropathological diagnosis). Secondary outcome was the association with tau pathology (determined using neuropathology or positron emission tomography [PET]).

Results  Mean age was 83.5 (SD, 8.5) years in cohort 1, 69.1 (SD, 10.3) years in cohort 2, and 35.8 (SD, 10.7) years in cohort 3; 38% were women in cohort 1, 51% in cohort 2, and 57% in cohort 3. In cohort 1, antemortem plasma P-tau217 differentiated neuropathologically defined AD from non-AD (area under the curve [AUC], 0.89 [95% CI, 0.81-0.97]) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P.15). In cohort 3, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers, compared with noncarriers, from approximately 25 years and older, which is 20 years prior to estimated onset of MCI among mutation carriers. Plasma P-tau217 levels correlated with tau tangles in participants with (Spearman ρ=0.64; P<.001), but not without (Spearman ρ=0.15; P=.33), β-amyloid plaques in cohort 1. In cohort 2, plasma P-tau217 discriminated abnormal vs normal tau-PET scans (AUC, 0.93 [95% CI, 0.91-0.96]) with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Aβ42:Aβ40 ratio, and MRI measures (AUC range, 0.67-0.90; P<.05), but its performance was not significantly different compared with CSF P-tau217 (AUC, 0.96; P=.22).

Conclusions and Relevance  Among 1402 participants from 3 selected cohorts, plasma P-tau217 discriminated AD from other neurodegenerative diseases, with significantly higher accuracy than established plasma- and MRI-based biomarkers, and its performance was not significantly different from key CSF- or PET-based measures. Further research is needed to optimize the assay, validate the findings in unselected and diverse populations, and determine its potential role in clinical care.

DOI: 10.1001/jama.2020.12134

Source: https://jamanetwork.com/journals/jama/fullarticle/2768841

JAMA-Journal of The American Medical Association:《美国医学会杂志》,创刊于1883年。隶属于美国医学协会,最新IF:51.273
官方网址:https://jamanetwork.com/
投稿链接:http://manuscripts.jama.com/cgi-bin/main.plex


本期文章:《美国医学会杂志》:Online/在线发表

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