Neurology Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Memory Clinic Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Neuroscience, Catholic University of the Sacred Heart, Rome, Italy.
Neurology Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Memory Clinic Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Neuroscience, Catholic University of the Sacred Heart, Rome, Italy.
Neurobiol Dis. 2023 Oct 1;186:106267. doi: 10.1016/j.nbd.2023.106267. Epub 2023 Aug 29.
CSF Neurofilament light chain(NfL) is a promising biomarker of neurodegeneration, but its utility in discriminating between Alzheimer's disease(AD) and frontotemporal dementia(FTD) is limited.
105 patients with clinical-biological diagnosis of mild cognitive impairment(MCI) due to AD (N = 72) or clinical diagnosis of FTD (N = 33) underwent neuropsychological assessment and CSF Aβ42/40, p-tau181, total-tau and NfL quantification. Group comparisons, correlations between continuous variables and ROC curve analysis were carried out to assess NfL role in discriminating between MCI due to AD and FTD, exploring the associations between NfL, ATN biomarkers and neuropsychological measures.
NfL levels were significantly lower in the AD group, while levels of total-tau were higher. In the FTD group, significant correlations were found between NfL, p-tau181 and total-tau, and between NfL and cognitive performances. In the AD group, NfL levels were directly correlated with total-tau and p-tau181; Aβ42/40 ratio was inversely correlated with total-tau and p-tau181, but not with NfL. Moreover, p-tau181 and t-tau levels were found to be associated with episodic memory and lexical-semantic impairment. Total-tau/NfL ratio differentiated prodromal-AD from FTD with an AUC of 0.951, higher than the individual measures.
DISCUSSION & CONCLUSIONS: The results support that NfL and total-tau levels reflect distinct pathophysiological neurodegeneration mechanisms, independent and dependent of Aβ pathology, respectively, Combining them may enhance both markers reliability, their ratio showing high accuracy in distinguishing MCI due to AD from FTD. Moreover, our results revealed associations between NfL and disease severity in FTD and between tauopathy and episodic memory and lexical-semantic impairment in prodromal-AD.
脑脊液神经丝轻链（NfL）是一种有前途的神经退行性疾病生物标志物，但在区分阿尔茨海默病（AD）和额颞叶痴呆（FTD）方面的效用有限。
105 名临床生物学诊断为 AD 引起的轻度认知障碍（MCI）的患者（N=72）或临床诊断为 FTD 的患者（N=33）接受了神经心理学评估和 CSF Aβ42/40、p-tau181、总 tau 和 NfL 定量检测。进行组间比较、连续变量之间的相关性和 ROC 曲线分析，以评估 NfL 在区分 AD 引起的 MCI 和 FTD 中的作用，探索 NfL、ATN 生物标志物和神经心理学测量之间的关联。
AD 组的 NfL 水平显著降低，而总 tau 水平升高。在 FTD 组中，NfL 与 p-tau181 和总 tau 之间，以及 NfL 与认知表现之间存在显著相关性。在 AD 组中，NfL 水平与总 tau 和 p-tau181 呈直接相关；Aβ42/40 比值与总 tau 和 p-tau181 呈负相关，但与 NfL 无关。此外，p-tau181 和 t-tau 水平与情景记忆和词汇语义障碍有关。总 tau/NfL 比值区分了前驱期 AD 和 FTD，AUC 为 0.951，高于单个指标。
结果支持 NfL 和总 tau 水平反映了不同的神经退行性病理生理学机制，分别独立于和依赖于 Aβ 病理学。将它们结合起来可以提高两种标志物的可靠性，它们的比值在区分 AD 引起的 MCI 和 FTD 方面具有很高的准确性。此外，我们的结果揭示了 FTD 中 NfL 与疾病严重程度之间的关系，以及前驱期 AD 中 tau 病变与情景记忆和词汇语义障碍之间的关系。
