Serum neurofilament light levels correlate with severity measures and neurodegeneration markers in autosomal dominant Alzheimer\u2019s disease

Raquel Sánchez-Valle,Martha S Foiani,Albert Lladó,Amanda Heslegrave,Nick C Fox,Anna Antonell,Beatriz Bosch,Mircea Balasa,Henrik Zetterberg

doi:10.1186/s13195-018-0439-y

Abstract

BackgroundBiomarkers that can track disease onset and progression in autosomal dominant Alzheimer’s disease (ADAD) are needed. We investigate whether serum neurofilament light (NfL) concentration is associated with clinical and cerebrospinal fluid (CSF) markers in ADAD. We also evaluate serum NfL differences between clinical groups.MethodsSerum NfL was measured cross-sectionally in 60 individuals from ADAD families using an ultrasensitive immunoassay on the Single molecule array (Simoa) platform and longitudinally in an exploratory study in a subset of six mutation carriers. Spearman coefficients assessed associations between serum NfL and relevant measures. Differences between groups were evaluated by Kruskal-Wallis and Mann-Whitney U tests.ResultsForty-two participants were mutation carriers: 22 symptomatic (SMC) and 20 asymptomatic (AMC). Eighteen subjects were non-carriers and cognitively normal (controls (CTR)). Serum NfL correlated with the estimated years from symptoms onset across mutation carriers (rho = 0.75, p < 0.001). In mutation carriers, serum NfL also showed strong correlation with clinical (rho = 0.70, p < 0.001) and cognitive (rho = −0.77, p < 0.001) measures and CSF NfL, total tau and phosphorylated tau levels (rho = 0.72, 0.71, and 0.71, respectively, all p < 0.001). Serum NfL concentration was higher in SMC than in AMC and CTR.ConclusionsSerum NfL might be a feasible non-invasive biomarker to track disease onset and severity in ADAD.

Highlights

Biomarkers that can track disease onset and progression in autosomal dominant Alzheimer’s disease (ADAD) are needed
No significant differences were observed between AMC and control population (CTR) in demographic, clinical, or biochemical variables included in Table 1 except for estimated years from symptom onset (EYO)
In mutation carriers (MC), serum neurofilament light (NfL) levels showed a negative correlation with Mini-Mental State Examination (MMSE; rho = −0.77, p < 0.001) and positive correlations with EYO and Clinical Dementia Rating (CDR) sum of boxes (CDR-SOB) (Fig. 1a-c and Table 2)

Summary

Introduction

Biomarkers that can track disease onset and progression in autosomal dominant Alzheimer’s disease (ADAD) are needed. We investigate whether serum neurofilament light (NfL) concentration is associated with clinical and cerebrospinal fluid (CSF) markers in ADAD. We evaluate serum NfL differences between clinical groups. Autosomal dominant Alzheimer’s disease (ADAD), with its almost 100% penetrance and relatively predictable age of onset, allows the evaluation of disease-modifying treatments at early or pre-symptomatic stages of the disease [1]. There is considerable interest in finding non-invasive biomarkers that could track the disease progression or provide evidence. We analysed serum NfL levels in a Spanish cohort of ADAD individuals and investigated whether they were associated with clinical markers of disease severity and CSF biomarkers Sánchez-Valle et al Alzheimer's Research & Therapy (2018) 10:113 supranuclear palsy [9], Huntington’s disease [10], and multiple sclerosis [11].

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