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

Cerebrospinal fluid biomarkers Episodic memory Neurodegeneration Neurofilaments (NfL) Semantic memory Total tau (t-tau)

Journal

Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169

Informations de publication

Date de publication:
01 10 2023
Historique:
received: 02 04 2023
revised: 10 08 2023
accepted: 22 08 2023
medline: 22 9 2023
pubmed: 1 9 2023
entrez: 31 8 2023
Statut: ppublish

Résumé

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. 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.

Identifiants

pubmed: 37652185
pii: S0969-9961(23)00282-6
doi: 10.1016/j.nbd.2023.106267
pii:
doi:

Substances chimiques

Biomarkers 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

106267

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest None.

Auteurs

Guido Maria Giuffrè (GM)

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.

Davide Quaranta (D)

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. Electronic address: davide.quaranta@unicatt.it.

Emanuele Maria Costantini (EM)

Neurology Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Salvatore Citro (S)

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.

Noemi Martellacci (N)

Memory Clinic Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Grazia De Ninno (G)

UOC of Chemistry, Biochemistry and Clinical Molecular Biology - Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Maria Gabriella Vita (MG)

Neurology Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Valeria Guglielmi (V)

Neurology Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Paolo Maria Rossini (PM)

Brain Connectivity Laboratory, Department of Neuroscience and Neurorehabilitation, IRCCS San Raffaele Roma, Rome, Italy.

Paolo Calabresi (P)

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.

Camillo Marra (C)

Memory Clinic Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Neuroscience, Catholic University of the Sacred Heart, Rome, Italy.

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Classifications MeSH