RT期刊文章SR电子T1 Blood-Based生物标志物的诊断性能和临床适用性前瞻记忆诊所队列摩根富林明神经学神经学乔FD Lippincott Williams &威尔金斯SP e860 OP e873 10.1212 / WNL。首页100签证官0000000000201597 8 A1乔迪Sarto A1拉奎尔Ruiz-Garcia Guillen A1 Nuria A1奥斯卡Ramos-Campoy A1该处Falgas A1戴安娜Esteller A1何塞·康塔A1瓜达卢佩费尔南德斯A1尤兰达冈萨雷斯A1 Adria Tort-Merino A1乔迪Junca-Parella A1 Bea博世A1塞尔吉Borrego-Ecija A1劳拉Molina-Porcel A1玛格达Castellvi A1米格尔·A1安娜Antonell A1约瑟玛丽亚·奥格A1劳拉Naranjo A1拉奎尔Sanchez-Valle A1艾伯特Llado A1,米尔卡Balasa年2023 UL //www.ez-admanager.com/content/100/8/e860.abstract AB背景和目标Blood-based生物标志物已成为微创的选择评估认知障碍。首页迄今为止,大多数研究评估他们在研究人群,限制日常临床实践的概括。我们评价他们的诊断性能和临床适用性。她们在一次前瞻性现实、记忆诊所队列。方法对所有的病人被怀疑是认知障碍2019年7月至2021年6月前瞻性邀请参加。五等离子体生物标志物(τ在苏氨酸磷酸化181 [p-tau181],胶质原纤维酸性蛋白(GFAP),神经丝轻链(NfL),总τ(t-tau)和泛素c端水解酶L1 [UCH-L1])测定与单分子阵列。性能评估相比,临床诊断(瞎了等离子体的结果)和淀粉样状态(CSF / PET)。一群没有认知能力受损(铜)控制也包括在内。结果三百四十九名参与者(平均年龄68,SD 8.3年)和36铜控制(平均年龄61.7岁,标准差8.2岁)被包括在内。在subcohort可用阿尔茨海默病(AD)生物标志物(n = 268),等离子体p-tau181和GFAP诊断精度高区分广告non-neurodegenerative原因(接受者操作特征曲线下面积0.94和0.92,分别),与p-tau181 GFAP表现系统。 Plasma p-tau181 levels predicted amyloid status (85% sensitivity and specificity) with accurate individual prediction in approximately 60% of the patients. Plasma NfL differentiated frontotemporal dementia (FTD) syndromes from CU (0.90) and non-neurodegenerative causes (0.93), whereas the discriminative capacity with AD and between all neurodegenerative and non-neurodegenerative causes was less accurate. A combination of p-tau181 and NfL identified FTD with 82% sensitivity and 85% specificity and had a negative predictive value for neurodegenerative diagnosis of 86%, ruling out half of the non-neurodegenerative diagnoses. In the subcohort without AD biomarkers, similar results were obtained. T-tau and UCH-L1 did not offer added diagnostic value.Discussion Plasma p-tau181 predicted amyloid status with high accuracy and could have potentially avoided CSF/amyloid PET testing in approximately 60% of subjects in a memory clinic setting. NfL was useful for identifying FTD from non-neurodegenerative causes but behaved worse than p-tau181 in all other comparisons. Combining p-tau181 and NfL improved diagnostic performance for FTD and non-neurodegenerative diagnoses. However, the 14% false-negative results suggest that further improvement is needed before implementation outside memory clinics.Classification of Evidence This study provides Class I evidence that plasma p-tau181 correlates with the presence or absence of AD and a combination of plasma p-tau181 and NfL correlates moderately well with a diagnosis of FTD.Aβ=β-amyloid; AD=Alzheimer disease; AUC=area under the ROC curve; bvFTD=behavioral variant FTD; CBS=corticobasal syndrome; CJD=Creutzfeldt-Jakob disease; CU=cognitively unimpaired; FTD=frontotemporal dementia; GFAP=glial fibrillary acidic protein; LBD=Lewy body dementia; MCI=mild cognitive impairment; MMSE=Mini-Mental State Examination; NfL=neurofilament light chain; nfPPA=nonfluent variant PPA; NPV=negative predictive value; PM=parsimonious model; PPA=primary progressive aphasia; PPV=positive predictive value; PSP=progressive supranuclear palsy; p-tau181=tau phosphorylated at threonine 181; ROC=receiver operating characteristic; SCD=subjective cognitive decline; SiMoA=single-molecule array; SND=suspected nondegenerative cognitive impairment; svPPA=semantic variant PPA; t-tau=total tau; UCH-L1=ubiquitin C-terminal hydrolase L1

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