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 A1342/40, 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; A1342/40 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 A13 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.

Giuffrè, G. M., Quaranta, D., Costantini, E. M., Citro, S., Martellacci, N., De Ninno, G., Vita, M. G., Guglielmi, V., Rossini, P. M., Calabresi, P., Marra, C., Cerebrospinal fluid neurofilament light chain and total-tau as biomarkers of neurodegeneration in Alzheimer's disease and frontotemporal dementia, <<NEUROBIOLOGY OF DISEASE>>, 2023; 186 (October): N/A-N/A. [doi:10.1016/j.nbd.2023.106267] [https://hdl.handle.net/10807/262388]

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

Quaranta, Davide;De Ninno, Grazia;Vita, Maria Gabriella;Guglielmi, Valeria;Calabresi, Paolo;Marra, Camillo
2023

Abstract

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 A1342/40, 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; A1342/40 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 A13 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.
2023
Inglese
Giuffrè, G. M., Quaranta, D., Costantini, E. M., Citro, S., Martellacci, N., De Ninno, G., Vita, M. G., Guglielmi, V., Rossini, P. M., Calabresi, P., Marra, C., Cerebrospinal fluid neurofilament light chain and total-tau as biomarkers of neurodegeneration in Alzheimer's disease and frontotemporal dementia, <<NEUROBIOLOGY OF DISEASE>>, 2023; 186 (October): N/A-N/A. [doi:10.1016/j.nbd.2023.106267] [https://hdl.handle.net/10807/262388]
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0969996123002826-main.pdf

accesso aperto

Tipologia file ?: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 968.85 kB
Formato Adobe PDF
968.85 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/262388
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact