Cerebrospinal fluid neurofilament light chain and total-tau as biomarkers of neurodegeneration in Alzheimer's disease and frontotemporal dementia.

INTRODUCTION: 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. METHODS: 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 Aß42/40, 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. RESULTS: 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; Aß42/40 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 Aß 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.

Associations Between Free and Cued Selective Reminding Test and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment.

Background: The Free and Cued Selective Reminding Test (FCSRT), assessing verbal episodic memory with controlled learning and semantic cueing, has been recommended for detecting the genuine encoding and storage deficits characterizing AD-related memory disorders. Objective: The present study aims at investigating the ability of FCSRT in predicting cerebrospinal fluid (CSF) evidence of amyloid-ß positivity in subjects with amnestic mild cognitive impairment (aMCI) and exploring its associations with amyloidopathy, tauopathy and neurodegeneration biomarkers. Methods: 120 aMCI subjects underwent comprehensive neurological and neuropsychological examinations, including the FCSRT assessment, and CSF collection; CSF Aß42/40 ratio, p-tau181, and total-tau quantification were conducted by an automated CLEIA method on Lumipulse G1200. Based on the Aß42/40 ratio value, subjects were classified as either A+ or A-. Results: All FCSRT subitem scores were significantly lower in A+ group and significantly predicted the amyloid-ß status, with Immediate Total Recall (ITR) being the best predictor. No significant correlations were found between FCSRT and CSF biomarkers in the A- aMCI group, while in the A+ aMCI group, all FCSRT subitem scores were negatively correlated with CSF p-tau181 and total-tau, but not with the Aß42/40 ratio. Conclusions: FCSRT confirms its validity as a tool for the diagnosis of AD, being able to predict the presence of amyloid-ß deposition with high specificity. The associations between FCSRT subitem scores and CSF p-tau-181 and total-tau levels in aMCI due to AD could further encourage the clinical use of this simple and cost-effective test in the evaluation of individuals with aMCI.