Serum neurofilament light chain in behavioral variant frontotemporal dementia

ObjectiveTo determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD).MethodsBlood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration–related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry.ResultsAt baseline, serum NfL level correlated with CSF NfL (bvFTDr= 0.706,p< 0.0001; AD/MCIr= 0.666,p= 0.0003). Highest serum levels were observed in bvFTD (p<0 0.0001 vs Con and MCI,p= 0.0078 vs AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with 91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL increased in bvFTD and AD (p= 0.0039 andp= 0.0006, respectively). At baseline and follow-up, NfL correlated with functional scores of patients with bvFTD (e.g., CDR-SOB [baseline]r= 0.4157,p= 0.0006; [follow-up]r= 0.5629,p< 0.0001) and with atrophy in the gray and white matter of many brain regions including frontal and subcortical areas (e.g., frontal lobe:r= −0.5857,p< 0.0001; 95% confidence interval −0.7415 to −0.3701). For patients with AD/MCI, NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline]r= 0.6624,p< 0.0001; [follow-up]r= 0.5659,p= 0.0003) but not with regional brain volumes.ConclusionsAs serum NfL correlates with functional impairment and brain atrophy in bvFTD at different disease stages, we propose it as marker of disease severity, paving the way for its future use as outcome measure for clinical trials.Classification of evidenceThis study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia.

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Plasma glial fibrillary acidic protein and neurofilament light chain for the diagnostic and prognostic evaluation of frontotemporal dementia

Translational Neurodegeneration ◽

10.1186/s40035-021-00275-w ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Nuole Zhu ◽

Miguel Santos-Santos ◽

Ignacio Illán-Gala ◽

Victor Montal ◽

Teresa Estellés ◽

...

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Cognitive Decline ◽

Frontotemporal Dementia ◽

Cortical Thickness ◽

Light Chain ◽

Diagnostic Performance ◽

Acidic Protein ◽

Neurofilament Light Chain ◽

Neurofilament Light

Abstract Background Astrocytes play an essential role in neuroinflammation and are involved in the pathogenesis of neurodenegerative diseases. Studies of glial fibrillary acidic protein (GFAP), an astrocytic damage marker, may help advance our understanding of different neurodegenerative diseases. In this study, we investigated the diagnostic performance of plasma GFAP (pGFAP), plasma neurofilament light chain (pNfL) and their combination for frontotemporal dementia (FTD) and Alzheimer’s disease (AD) and their clinical utility in predicting disease progression. Methods pGFAP and pNfL concentrations were measured in 72 FTD, 56 AD and 83 cognitively normal (CN) participants using the Single Molecule Array technology. Of the 211 participants, 199 underwent cerebrospinal (CSF) analysis and 122 had magnetic resonance imaging. We compared cross-sectional biomarker levels between groups, studied their diagnostic performance and assessed correlation between CSF biomarkers, cognitive performance and cortical thickness. The prognostic performance was investigated, analyzing cognitive decline through group comparisons by tertile. Results Unlike pNfL, which was increased similarly in both clinical groups, pGFAP was increased in FTD but lower than in AD (all P < 0.01). Combination of both plasma markers improved the diagnostic performance to discriminate FTD from AD (area under the curve [AUC]: combination 0.78; pGFAP 0.7; pNfL 0.61, all P < 0.05). In FTD, pGFAP correlated with cognition, CSF and plasma NfL, and cortical thickness (all P < 0.05). The higher tertile of pGFAP was associated with greater change in MMSE score and poor cognitive outcome during follow-up both in FTD (1.40 points annually, hazard ratio [HR] 3.82, P < 0.005) and in AD (1.20 points annually, HR 2.26, P < 0.005). Conclusions pGFAP and pNfL levels differ in FTD and AD, and their combination is useful for distinguishing between the two diseases. pGFAP could also be used to track disease severity and predict greater cognitive decline during follow-up in patients with FTD.

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Relationship between serum neurofilament light chain levels and cognitive decline over 9-years follow-up in patients after first demyelinating event suggestive of MS

10.26226/morressier.5b75785e5aff7400151f3465 ◽

2018 ◽

Author(s):

Tomas Uher ◽

Dana Horakova

Keyword(s):

Cognitive Decline ◽

Light Chain ◽

Neurofilament Light Chain ◽

Neurofilament Light

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Fatigue in Patients With Multiple System Atrophy

Neurology ◽

10.1212/wnl.0000000000012968 ◽

2021 ◽

Vol 98 (1) ◽

pp. e73-e82

Author(s):

Lingyu Zhang ◽

Bei Cao ◽

Yanbing Hou ◽

Xiaojing Gu ◽

Qian-Qian Wei ◽

...

Keyword(s):

Multiple System Atrophy ◽

Regression Model ◽

Rating Scale ◽

Early Stage ◽

Progression Rate ◽

Nonmotor Symptoms ◽

Binary Logistic Regression Model ◽

Neurofilament Light Chain ◽

Neurofilament Light

Background and ObjectivesNonmotor symptoms are common in patients with multiple system atrophy (MSA), but there is limited knowledge regarding fatigue in MSA. This study aimed to investigate the frequency and evolution of fatigue and the factors related to fatigue and its progression in patients with MSA at an early stage.MethodsPatients with probable MSA were comprehensively evaluated at both baseline and the 1-year follow-up, including their motor and nonmotor symptoms. Fatigue and anxiety were assessed using the Fatigue Severity Scale (FSS) and Hamilton Anxiety Rating Scale (HARS), respectively. Orthostatic hypotension (OH) was defined as a decrease in the systolic or diastolic blood pressure by at least 30 and 15 mm Hg, respectively. The binary logistic regression model and linear regression model were used to analyze the factors related to fatigue and its progression, respectively.ResultsThis study enrolled 146 patients with MSA. The frequency of fatigue was 60.3%, 55.1%, and 64.9% in MSA, MSA with predominant parkinsonism (MSA-P), and MSA with predominant cerebellar ataxia (MSA-C), respectively. The frequency of fatigue and the FSS score in patients with MSA increased from baseline to the 1-year follow-up (p < 0.05). Young age (odds ratio [OR] 0.939, 95% confidence interval [CI] 0.894–0.987), OH (OR 2.806, 95% CI 1.253–6.286), and high HARS score (OR 1.014, 95% CI 1.035–1.177) were associated with fatigue in MSA. OH was associated with fatigue in MSA-P (OR 3.391, 95% CI 1.066–10.788), while high HARS score was associated with fatigue in MSA-C (OR 1.159, 95% CI 1.043–1.287). In addition, only low FSS scores at baseline were associated with the annual progression rate of FSS scores in MSA, MSA-P, and MSA-C (p < 0.05). Neurofilament light chain, α-synuclein, glial fibrillary acidic protein, brain-derived neurotrophic factor, and triggering receptor expressed on myeloid cell-2 were not significantly associated with fatigue and its progression in MSA.DiscussionFatigue was prevalent in early-stage MSA, and it increased and remained persistent over time. This study demonstrated that OH and anxiety were associated with fatigue in patients with MSA.

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Prediagnostic Neurofilament Light Chain Levels in Amyotrophic Lateral Sclerosis

Neurology ◽

10.1212/wnl.0000000000012632 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012632

Author(s):

Kjetil Bjornevik ◽

Eilis J. O'Reilly ◽

Samantha Molsberry ◽

Laurence N. Kolonel ◽

Loic Le Marchand ◽

...

Keyword(s):

Light Chain ◽

Conditional Logistic Regression ◽

Disease Diagnosis ◽

Health Study ◽

Plasma Samples ◽

Blood Draw ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Rate Ratios

Objective:To assess whether plasma neurofilament light chain (NfL) levels are elevated before ALS diagnosis and to evaluate whether pre-diagnostic NfL levels are associated with metabolic alterations.Methods:We conducted a matched case-control study nested in three large prospective US cohorts (the Nurses’ Health Study, the Health Professionals Follow-up Study, and the Multiethnic Cohort Study), and identified 84 individuals who developed ALS during follow-up and had available plasma samples prior to disease diagnosis. For each ALS case, we randomly selected controls from those who were alive at the time of the case diagnosis and matched on birth year, sex, race/ethnicity, fasting status, cohort, and time of blood draw. We measured NfL in the plasma samples and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for ALS, adjusting for body mass index, smoking, physical activity, and urate levels.Results:Higher NfL levels were associated with a higher ALS risk in plasma samples collected within 5 years of the ALS diagnosis (RR per 1 standard deviation [SD] increase: 2.68, 95% CI: 1.18-6.08), but not in samples collected further away from the diagnosis (RR per 1 SD increase 1.16, 95% CI: 0.78-1.73). A total of 21 metabolites were correlated with pre-diagnostic NfL levels in ALS cases (p < 0.05), but none of these remained significant after multiple comparison adjustments.Conclusions:Plasma NfL levels were elevated in pre-diagnostic ALS cases, indicating that NfL may be a useful biomarker already in the earliest stages of the disease.Classification of Evidence:This study provides Class II evidence that plasma NfL levels are elevated in pre-diagnostic ALS patients.

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