Plasma tau is increased in frontotemporal dementia.
Plasma tau is increased in frontotemporal dementia.
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DOI：
10.1136/jnnp-2017-317260
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Rohrer JD
中科院分区：
文献类型：
--
作者：
Foiani MS;Woollacott IO;Heller C;Bocchetta M;Heslegrave A;Dick KM;Russell LL;Marshall CR;Mead S;Schott JM;Fox NC;Warren JD;Zetterberg H;Rohrer JD
额颞叶痴呆（FTD）是一种异质性神经退行性疾病，临床表现为人格改变（行为变异型FTD（bvFTD））或语言缺陷（原发性进行性失语症（PPA））。大约三分之一的FTD是家族性的，GRN、MAPT和C9 orf 72突变是主要的遗传原因。FTD中仍然缺乏基础病理学的稳健生物标志物，目前没有标志物能够区分生活中的tau和TDP-43包涵体。本研究使用超灵敏单分子方法测量了176例受试者的血浆tau浓度：71例bvFTD受试者、83例PPA受试者和22例健康对照者。患者组包括36例MAPT（n=12）、GRN（n=9）或C9 orf 72（n=15）致病突变患者。使用线性回归模型和偏倚校正的bootstrap CI在临床和遗传组与对照组之间进行组比较。进行相关性分析以研究与疾病严重程度和进展的相关性。与对照组（1.67（0.50）pg/mL）相比，bvFTD（平均1.96（SD 1.07）pg/mL）和PPA（2.65（2.15）pg/mL）中观察到较高的血浆tau浓度。调查PPA组进一步显示，与对照组相比，PPA亚型中的每一种（非流利、语义和逻辑开放变体，以及不符合三种主要变体之一标准的第四组）的水平显著更高。在遗传组中，与对照组相比，仅MAPT组的浓度显著增加（2.62（1.39）pg/mL）。与横断面或纵向脑体积、血清神经丝轻链浓度或病程无显著相关性。在所有临床组中，FTD的血浆tau水平均升高，但仅在MAPT突变的遗传亚型中升高，即在尸检时明确存在tau病理学的患者组。需要在病理学证实的队列中开展进一步研究，以进一步研究这种关联，以及血浆tau是否有助于区分伴有tau的FTD患者与伴有其他病理学的患者。
Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder presenting clinically with personality change (behavioural variant FTD (bvFTD)) or language deficits (primary progressive aphasia (PPA)). About a third of FTD is familial with mutations in GRN, MAPT and C9orf72 being the major genetic causes. Robust biomarkers of the underlying pathology are still lacking in FTD with no markers currently being able to distinguish those with tau and TDP-43 inclusions during life. This study used an ultrasensitive single molecule methodology to measure plasma tau concentrations in 176 participants: 71 with bvFTD, 83 with PPA and 22 healthy controls. The patient group included 36 with pathogenic mutations in either MAPT (n=12), GRN (n=9) or C9orf72 (n=15). Group comparisons were performed between clinical and genetic groups and controls using a linear regression model with bias-corrected bootstrap CIs. Correlative analyses were performed to investigate associations with measures of disease severity and progression. Higher plasma tau concentrations were seen in bvFTD (mean 1.96 (SD 1.07) pg/mL) and PPA (2.65 (2.15) pg/mL) compared with controls (1.67 (0.50) pg/mL). Investigating the PPA group further showed significantly higher levels compared with controls in each of the PPA subtypes (non-fluent, semantic and logopenic variants, as well as a fourth group not meeting criteria for one of the three main variants). In the genetic groups, only the MAPT group had significantly increased concentrations (2.62 (1.39) pg/mL) compared with controls. No significant correlations were seen with cross-sectional or longitudinal brain volumes, serum neurofilament light chain concentrations or disease duration. Plasma tau levels are increased in FTD in all clinical groups, but in the genetic subtypes only in MAPT mutations, the group of patients who definitively have tau pathology at postmortem. Future studies will be required in pathologically confirmed cohorts to investigate this association further, and whether plasma tau will be helpful in differentiating patients with FTD with tau from those with other pathologies.
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发表时间：
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期刊：
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影响因子：
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作者：
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10.1080/21678421.2016.1267768
发表时间：
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影响因子：
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