Anuschka Silva-Spínola1,2, Marisa Lima1,3,4, Maria João Leitão1, João Durães1,3,5, Miguel Tábuas-Pereira1,3,5, Maria Rosário Almeida1, Isabel Santana1,3,5, Inês Baldeiras1,5. 1. Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal. 2. Department of Informatics Engineering, Centre for Informatics and Systems, University of Coimbra, Coimbra, Portugal. 3. Neurology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. 4. Faculty of Psychology and Educational Sciences, Center for Research in Neuropsychology and Cognitive Behavioral Intervention (CINEICC), University of Coimbra, Coimbra, Portugal. 5. Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Abstract
BACKGROUND AND PURPOSE: Neurofilament light chain (NfL) has recently been proposed as a promising biomarker in frontotemporal dementia (FTD). We investigated the correlation of both cerebrospinal fluid (CSF) and serum NfL with detailed neuropsychological data and cognitive decline in a cohort of sporadic and familial FTD. METHODS: CSF and serum NfL, as well as conventional CSF Alzheimer's disease (AD) biomarkers (Aβ42, t-Tau, p-Tau181), were determined in 63 FTD patients (30 sporadic-FTD, 20 with progranulin (GRN) mutations [FTD-GRN], 13 with chromosome 9 open reading frame 72 [C9orf72] expansions [C9orf72-FTD]), 37 AD patients, and 31 neurologic controls. Serum NfL was also quantified in 37 healthy individuals. Correlations between baseline CSF and serum NfL levels, standardized neuropsychological tests, and the rate of cognitive decline in FTD patients were assessed. RESULTS: CSF and serum NfL presented with significantly higher levels in FTD than in AD patients and both control groups. Within FTD subtypes, genetic cases, and particularly FTD-GRN, had higher CSF and serum NfL levels. Significant correlations between NfL levels and overall cognitive function, abstract reasoning (CSF and serum), executive functions, memory, and language (serum) were found. A relationship between increased baseline CSF and serum NfL and a decay in cognitive performance over time was also observed. CONCLUSIONS: Our findings highlight the potential of serum NfL as a useful surrogate end point of disease severity in upcoming targeted treatments.
BACKGROUND AND PURPOSE: Neurofilament light chain (NfL) has recently been proposed as a promising biomarker in frontotemporal dementia (FTD). We investigated the correlation of both cerebrospinal fluid (CSF) and serum NfL with detailed neuropsychological data and cognitive decline in a cohort of sporadic and familial FTD. METHODS: CSF and serum NfL, as well as conventional CSF Alzheimer's disease (AD) biomarkers (Aβ42, t-Tau, p-Tau181), were determined in 63 FTD patients (30 sporadic-FTD, 20 with progranulin (GRN) mutations [FTD-GRN], 13 with chromosome 9 open reading frame 72 [C9orf72] expansions [C9orf72-FTD]), 37 AD patients, and 31 neurologic controls. Serum NfL was also quantified in 37 healthy individuals. Correlations between baseline CSF and serum NfL levels, standardized neuropsychological tests, and the rate of cognitive decline in FTD patients were assessed. RESULTS: CSF and serum NfL presented with significantly higher levels in FTD than in AD patients and both control groups. Within FTD subtypes, genetic cases, and particularly FTD-GRN, had higher CSF and serum NfL levels. Significant correlations between NfL levels and overall cognitive function, abstract reasoning (CSF and serum), executive functions, memory, and language (serum) were found. A relationship between increased baseline CSF and serum NfL and a decay in cognitive performance over time was also observed. CONCLUSIONS: Our findings highlight the potential of serum NfL as a useful surrogate end point of disease severity in upcoming targeted treatments.