Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau-Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers.
Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau-Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers.
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DOI：
10.1001/jamaneurol.2017.0655
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发表时间：
2017-09-01
期刊：
影响因子：
29
通讯作者：
Vassar MJ
中科院分区：
文献类型：
--
作者：
Rubenstein R;Chang B;Yue JK;Chiu A;Winkler EA;Puccio AM;Diaz-Arrastia R;Yuh EL;Mukherjee P;Valadka AB;Gordon WA;Okonkwo DO;Davies P;Agarwal S;Lin F;Sarkis G;Yadikar H;Yang Z;Manley GT;Wang KKW;the TRACK-TBI Investigators;Cooper SR;Dams-O'Connor K;Borrasso AJ;Inoue T;Maas AIR;Menon DK;Schnyer DM;Vassar MJ
在美国，每年至少有350万人因创伤性脑损伤（TBI）寻求医疗护理。TBI治疗的发展受到缺乏诊断和预后生物标志物的限制。微管相关蛋白tau是一种轴突磷蛋白。迄今为止，尚未研究急性TBI和慢性TBI患者血浆中低磷酸化tau蛋白（P-tau）的存在。检查血浆P-tau和总-tau（T-tau）水平与急性和慢性TBI中损伤的存在、严重程度、病理解剖损伤类型（神经影像学）以及患者结局之间的关系。在TRACK-TBI初步研究中，在单个时间点从3个I级创伤中心收治的196名急性TBI患者（伤后<24小时）和住院康复单位收治的21名TBI患者（平均值[SD]，伤后176.4 [44.5]天）中收集血浆。对照样品购自商业供应商。TRACK-TBI初步研究于2010年4月1日至2012年6月30日进行。本研究的数据分析于2015年8月1日至2017年3月13日进行。使用结合滚环扩增的超高灵敏度基于激光的免疫测定多阵列光纤，测定血浆样品的P-tau（使用特异性识别磷酸苏氨酸-231的抗体）和T-tau。在217例TBI患者中，161例（74.2%）为男性;平均（SD）年龄为42.5（18.1）岁。急性TBI组P-tau、T-tau水平及P-tau-T-tau比值均高于健康对照组。3个tau指数的受试者操作特征分析表明，曲线下面积（AUC）分别为1.000、0.916和1.000，用于区分轻度TBI（格拉斯哥昏迷量表[GCS]评分，13-15，n = 162）与健康对照的准确性。P-tau水平和P-tau-T-tau比率在更严重的TBI个体中更高（GCS，≤12 vs 13-15）。P-tau水平和P-tau-T-tau比值在区分头颅CT阳性和阴性病例方面优于T-tau水平（AUC分别为0.921、0.923和0.646）。急性P-tau水平和P-tau-T-tau比率弱区分具有良好结局的TBI患者（格拉斯哥结局量表扩展GOS-E，7-8）（AUC分别为0.663和0.658）和鉴定具有不良结局的患者（GOS-E，≤4 vs >4）（AUC分别为0.771和0.777）。来自慢性TBI患者的血浆样品也显示出升高的P-tau水平和显著高于健康对照的P-tau-T-tau比率，两个P-tau指数强烈区分慢性TBI患者和健康对照（AUC分别为1.000和0.963）。血浆P-tau水平和P-tau-T-tau比值优于T-tau水平作为急性TBI的诊断和预后生物标志物。与单独的T-tau水平相比，P-tau水平和P-tau-T-tau比率在慢性TBI患者中显示出更稳健和持续的升高。
Annually in the United States, at least 3.5 million people seek medical attention for traumatic brain injury (TBI). The development of therapies for TBI is limited by the absence of diagnostic and prognostic biomarkers. Microtubule-associated protein tau is an axonal phosphoprotein. To date, the presence of the hypophosphorylated tau protein (P-tau) in plasma from patients with acute TBI and chronic TBI has not been investigated. To examine the associations between plasma P-tau and total-tau (T-tau) levels and injury presence, severity, type of pathoanatomic lesion (neuroimaging), and patient outcomes in acute and chronic TBI. In the TRACK-TBI Pilot study, plasma was collected at a single time point from 196 patients with acute TBI admitted to 3 level I trauma centers (<24 hours after injury) and 21 patients with TBI admitted to inpatient rehabilitation units (mean [SD], 176.4 [44.5] days after injury). Control samples were purchased from a commercial vendor. The TRACK-TBI Pilot study was conducted from April 1, 2010, to June 30, 2012. Data analysis for the current investigation was performed from August 1, 2015, to March 13, 2017. Plasma samples were assayed for P-tau (using an antibody that specifically recognizes phosphothreonine-231) and T-tau using ultra-high sensitivity laser-based immunoassay multi-arrayed fiberoptics conjugated with rolling circle amplification. In the 217 patients with TBI, 161 (74.2%) were men; mean (SD) age was 42.5 (18.1) years. The P-tau and T-tau levels and P-tau–T-tau ratio in patients with acute TBI were higher than those in healthy controls. Receiver operating characteristic analysis for the 3 tau indices demonstrated accuracy with area under the curve (AUC) of 1.000, 0.916, and 1.000, respectively, for discriminating mild TBI (Glasgow Coma Scale [GCS] score, 13–15, n = 162) from healthy controls. The P-tau level and P-tau–T-tau ratio were higher in individuals with more severe TBI (GCS, ≤12 vs 13–15). The P-tau level and P-tau–T-tau ratio outperformed the T-tau level in distinguishing cranial computed tomography–positive from −negative cases (AUC = 0.921, 0.923, and 0.646, respectively). Acute P-tau levels and P-tau–T-tau ratio weakly distinguished patients with TBI who had good outcomes (Glasgow Outcome Scale–Extended GOS-E, 7–8) (AUC = 0.663 and 0.658, respectively) and identified those with poor outcomes (GOS-E, ≤4 vs >4) (AUC = 0.771 and 0.777, respectively). Plasma samples from patients with chronic TBI also showed elevated P-tau levels and a P-tau–T-tau ratio significantly higher than that of healthy controls, with both P-tau indices strongly discriminating patients with chronic TBI from healthy controls (AUC = 1.000 and 0.963, respectively). Plasma P-tau levels and P-tau–T-tau ratio outperformed T-tau level as diagnostic and prognostic biomarkers for acute TBI. Compared with T-tau levels alone, P-tau levels and P-tau–T-tau ratios show more robust and sustained elevations among patients with chronic TBI.
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影响因子：
17.1
作者：
Goldstein LE;Fisher AM;Tagge CA;Zhang XL;Velisek L;Sullivan JA;Upreti C;Kracht JM;Ericsson M;Wojnarowicz MW;Goletiani CJ;Maglakelidze GM;Casey N;Moncaster JA;Minaeva O;Moir RD;Nowinski CJ;Stern RA;Cantu RC;Geiling J;Blusztajn JK;Wolozin BL;Ikezu T;Stein TD;Budson AE;Kowall NW;Chargin D;Sharon A;Saman S;Hall GF;Moss WC;Cleveland RO;Tanzi RE;Stanton PK;McKee AC
通讯作者：
McKee AC
DOI：
10.1186/s13195-014-0068-z
发表时间：
2014
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Montenigro PH;Baugh CM;Daneshvar DH;Mez J;Budson AE;Au R;Katz DI;Cantu RC;Stern RA
通讯作者：
Stern RA
影响因子：
3.3
作者：
Park, S. -Y.;Tournell, C.;Ferreira, A.
通讯作者：
Ferreira, A.
影响因子：
1
作者：
Omalu, Bennet I;Hamilton, Ronald L;Bailes, Julian
通讯作者：
Bailes, Julian
影响因子：
1
作者：
Omalu, Bennet I;Fitzsimmons, Robert P;Bailes, Julian
通讯作者：
Bailes, Julian