TY - T1的诊断性能和临床适用性Blood-Based生物标志物的前瞻记忆诊所队列JF -神经学乔-神经病学SP - e860 LP - e873做- 10.1212 / WNL。首页0000000000201597六世- 100 - 8盟乔迪Sarto盟Nuria吉兰-拉奎尔Ruiz-Garcia盟盟-奥斯卡Ramos-Campoy盟该处Falgas盟——戴安娜Esteller盟——何塞·康塔AU -瓜达卢佩费尔南德斯AU -尤兰达冈萨雷斯盟-阿德里亚Tort-Merino AU -乔迪Junca-Parella盟Bea博世AU -塞尔吉Borrego-Ecija AU -劳拉Molina-Porcel AU -玛格达Castellvi AU -米盖尔范盖拉盟安娜Antonell AU -何塞玛丽亚·奥格盟-劳拉Naranjo AU -拉奎尔Sanchez-Valle AU -阿尔伯特Llado盟米尔卡Balasa Y1 - 2023/02/21 UR - //www.ez-admanager.com/content/100/8/e860.abstract N2 -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 ER -