Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Nov 3;10(1):113.
doi: 10.1186/s13195-018-0439-y.

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

Raquel Sánchez-Valle  1 , Amanda Heslegrave  2   3 , Martha S Foiani  2   3 , Beatriz Bosch  4 , Anna Antonell  4 , Mircea Balasa  4 , Albert Lladó  4 , Henrik Zetterberg  2   3   5   6 , Nick C Fox  3   7
Affiliations

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

Raquel Sánchez-Valle et al. Alzheimers Res Ther. .

Abstract

Background: 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 also evaluate serum NfL differences between clinical groups.

Methods: Serum 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.

Results: Forty-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.

Conclusions: Serum NfL might be a feasible non-invasive biomarker to track disease onset and severity in ADAD.

Keywords: Alzheimer’s disease; Biomarkers; Familial Alzheimer’s disease; Neurofilament light; Presenilin 1.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Hospital Clinic of Barcelona ethics committee (HCB/2012/7476) and all subjects gave written informed consent.

Consent for publication

Not applicable.

Competing interests

HZ has served on advisory boards for Roche Diagnostics and Eli Lilly, has received travel support from Teva, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg, Sweden. NCF has received fees (paid to University College London) for consultancy from Eli Lilly, Novartis, Sanofi, Roche/Genentech, and GlaxoSmithKline, and for serving on a Data Monitoring Committee for Biogen. The remaining authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Correlations of serum neurofilament light (NfL) levels with relevant variables in mutation carriers. a Estimated years to/from symptom onset (EYO), b Mini-Mental State Examination (MMSE), c Clinical Dementia Rating sum of boxes (CDR-SOB), d cerebrospinal fluid (CSF) NfL, e CSF total tau (T-tau), and f CSF phosphorylated tau (Ptau)
Fig. 2
Fig. 2
Individual paired (basal + longitudinal) serum neurofilament light (NfL) levels. EYO estimated years to/from symptom onset. MC mutation carriers
See this image and copyright information in PMC

References

    1. Bateman RJ, Aisen PS, De Strooper B, Fox NC, Lemere CA, Ringman JM, et al. Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease. Alzheimers Res Ther. 2011;3(1):1. doi: 10.1186/alzrt59. - DOI - PMC - PubMed
    1. Carrillo MC, Brashear HR, Logovinsky V, Ryan JM, Feldman HH, Siemers ER, et al. Can we prevent Alzheimer's disease? Secondary "prevention" trials in Alzheimer's disease. Alzheimers Dement. 2013;9:123–131. doi: 10.1016/j.jalz.2012.12.004. - DOI - PubMed
    1. Mills SM, Mallmann J, Santacruz AM, Fuqua A, Carril M, Aisen PS, et al. Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial. Rev Neurol (Paris) 2013;169:737–743. doi: 10.1016/j.neurol.2013.07.017. - DOI - PMC - PubMed
    1. Fagan AM, Xiong C, Jasielec MS, Bateman RJ, Goate AM, Benzinger TL, et al. Longitudinal change in CSF biomarkers in autosomal-dominant Alzheimer's disease. Sci Transl Med. 2014;6(226):226ra30. doi: 10.1126/scitranslmed.3007901. - DOI - PMC - PubMed
    1. Fortea J, Lladó A, Bosch B, Antonell A, Oliva R, Molinuevo JL, Sánchez-Valle R. Cerebrospinal fluid biomarkers in Alzheimer's disease families with PSEN1 mutations. Neurodegener Dis. 2011;8:202–207. doi: 10.1159/000322229. - DOI - PubMed

Publication types