血漿磷酸化-tau蛋白217可準確鑑別阿爾茨海默病
作者：
小柯機器人發布時間：2020/7/29 22:44:06
瑞典斯科訥大學醫院Oskar Hansson團隊分析了血漿磷酸化-tau蛋白217鑑別阿爾茨海默病和其他神經退行性疾病的準確性。2020年7月28日，該研究發表在《美國醫學會雜誌》上。
目前阿爾茨海默病（AD）的診斷檢測方法存在局限性。為了檢驗血漿中217號蘇氨酸磷酸化的tau蛋白（P-tau217）作為生物標誌物診斷AD的準確性，研究組進行了一項橫斷面研究。
2007年5月至2019年1月，研究組在美國亞利桑那州招募了34名AD患者和47名非AD參與者（隊列1）；2017年4月至2019年9月，在瑞典招募了301例無認知障礙的參與者，178例輕度認知障礙（MCI）者，121例AD痴呆患者，99例其他神經退行性疾病患者（隊列2）；2013年12月至2017年2月，在哥倫比亞招募了364例PSEN1 E280A突變攜帶者和257例突變非攜帶者（隊列3）。
隊列1的平均年齡為83.5歲，隊列2為69.1歲，隊列3為35.8歲。隊列1中女性佔38%，隊列2為51%，隊列3為57%。隊列1中血漿P-tau217可將神經病理學定義的AD與非AD區別開，曲線下面積（AUC）為0.89，準確性明顯高於血漿P-tau181和神經絲輕鏈（NfL）。
隊列2中血漿P-tau217對臨床AD痴呆與其他神經退行性疾病的診斷準確性（AUC為0.96）顯著高於血漿P-tau181、血漿NfL和MRI測量值，但與腦脊液（CSF）P-tau217、CSF P-tau181和tau-PET相比沒有顯著差異。隊列3中，從大約25歲及以上開始，PSEN1突變攜帶者中的血漿P-tau217水平顯著高於非攜帶者，比攜帶者預計的MCI發病時間早了20年。
隊列1中，參與者血漿P-tau217水平與tau蛋白纏結相關，但與β-澱粉樣斑塊無關。隊列2中，血漿P-tau217可區分異常與正常tau-PET掃描（AUC為0.93），其準確度明顯高於血漿P-tau181、血漿NfL、CSF P-tau181、CSF Aβ42 ：Aβ40比值和MRI測量值，但與CSF P-tau217相比無顯著差異。
總之，血漿P-tau217可將AD與其他神經退行性疾病區別開來，其準確度明顯高於基於血漿和MRI的生物標誌物，但與基於CSF或PET的關鍵指標相比並無顯著差異。
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