van Engelen Marie-Paule E, Heijst Hans, Willemse Eline A J, Oudega Mardien L, Vermunt Lisa, Scheltens Philip, Vijverberg Everard G B, Pijnenburg Yolande A L, Teunissen Charlotte E
Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, Noord-Holland 1081 HZ, The Netherlands.
Amsterdam Neuroscience, Neurodegeneration, Amsterdam, Noord-Holland 1081 HV, The Netherlands.
Brain Commun. 2023 Apr 12;5(2):fcad120. doi: 10.1093/braincomms/fcad120. eCollection 2023.
clinical overlap of frontotemporal dementia and primary psychiatric diseases hampers diagnostic distinction, leading to frequent misdiagnosis and diagnostic delay. Neurofilament light chain has shown great potential in CSF and blood for the distinction of frontotemporal dementia from primary psychiatric diseases. Measurement of neurofilament light chain in urine would be even more patient-friendly. We aimed to test the performance of neurofilament light chain urine measurements for diagnostics in frontotemporal dementia and to assess their correlation with serum levels. Fifty-five subjects ( = 19 frontotemporal dementia, = 19 primary psychiatric diseases and = 17 controls) were included with available paired urine and serum samples. All subjects underwent standardized extensive diagnostic assessment. Samples were analysed with the ultrasensitive single molecule array neurofilament light chain assay. Neurofilament light chain group comparisons were performed adjusted for age, sex and geriatric depression scale. In the majority of the cohort, neurofilament light chain concentrations were not detectable in urine ( = 6 samples above lower limit of detection (0.038 pg/ml): = 5 frontotemporal dementia, = 1 primary psychiatric disease). The frequency of a detectable neurofilament light chain level in urine in the frontotemporal dementia group did not differ from psychiatric disorders (Fisher Exact-test = 0.180). In the individuals with detectable urine neurofilament light chain values, there was no correlation between the urine and serum neurofilament light chain levels. As expected, serum neurofilament light chain levels were higher in frontotemporal dementia compared to primary psychiatric diseases and controls ( < 0.001), adjusted for age, sex and geriatric depression scale. Receiver operating characteristic curve analysis of serum neurofilament light chain of frontotemporal dementia versus primary psychiatric diseases showed an area under the curve of 0.978 95% confidence interval 0.941-1.000, < 0.001. Urine is not suitable as a matrix for neurofilament light chain analysis and serum neurofilament light chain is still the most patient-friendly matrix for differentiation between frontotemporal dementia and primary psychiatric diseases.
额颞叶痴呆与原发性精神疾病在临床上的重叠阻碍了诊断区分，导致频繁误诊和诊断延迟。神经丝轻链在脑脊液和血液中显示出区分额颞叶痴呆与原发性精神疾病的巨大潜力。尿液中神经丝轻链的检测对患者来说更加便捷。我们旨在测试尿液中神经丝轻链检测在额颞叶痴呆诊断中的性能，并评估其与血清水平的相关性。纳入了55名受试者（19名额颞叶痴呆患者、19名原发性精神疾病患者和17名对照），他们均有可用的配对尿液和血清样本。所有受试者均接受了标准化的全面诊断评估。样本采用超灵敏单分子阵列神经丝轻链检测法进行分析。神经丝轻链组间比较在调整年龄、性别和老年抑郁量表后进行。在大多数队列中，尿液中未检测到神经丝轻链浓度（6份样本高于检测下限（0.038 pg/ml）：5份为额颞叶痴呆患者，1份为原发性精神疾病患者）。额颞叶痴呆组尿液中可检测到神经丝轻链水平的频率与精神疾病组无差异（Fisher精确检验P = 0.180）。在尿液神经丝轻链值可检测到的个体中，尿液和血清神经丝轻链水平之间无相关性。正如预期的那样，在调整年龄、性别和老年抑郁量表后，额颞叶痴呆患者的血清神经丝轻链水平高于原发性精神疾病患者和对照组（P < 0.001）。额颞叶痴呆与原发性精神疾病患者血清神经丝轻链的受试者工作特征曲线分析显示，曲线下面积为0.978（95%置信区间0.941 - 1.000，P < 0.001）。尿液不适宜作为神经丝轻链分析的基质，血清神经丝轻链仍是区分额颞叶痴呆与原发性精神疾病最便捷的基质。
