Cited by 245Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchAmyotrophic Lateral Sclerosis Research

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

Serum neurofilament light in familial Alzheimer disease: A marker of early neurodegeneration

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Abstract

Objectives: To investigate whether serum neurofilament light (NfL) concentration is increased in familial Alzheimer disease (FAD), both pre and post symptom onset, and whether it is associated with markers of disease stage and severity. Methods: We recruited 48 individuals from families with PSEN1 or APP mutations to a cross-sectional study: 18 had symptomatic Alzheimer disease (AD) and 30 were asymptomatic but at 50% risk of carrying a mutation. Serum NfL was measured using an ultrasensitive immunoassay on the single molecule array (Simoa) platform. Cognitive testing and MRI were performed; 33 participants had serial MRI, allowing calculation of atrophy rates. Genetic testing established mutation status. A generalized least squares regression model was used to compare serum NfL among symptomatic mutation carriers, presymptomatic carriers, and noncarriers, adjusting for age and sex. Spearman coefficients assessed associations between serum NfL and (1) estimated years to/from symptom onset (EYO), (2) cognitive measures, and (3) MRI measures of atrophy. Results: Nineteen of the asymptomatic participants were mutation carriers (mean EYO −9.6); 11 were noncarriers. Compared with noncarriers, serum NfL concentration was higher in both symptomatic (p < 0.0001) and presymptomatic mutation carriers (p = 0.007). Across all mutation carriers, serum NfL correlated with EYO (ρ = 0.81, p < 0.0001) and multiple cognitive and imaging measures, including Mini-Mental State Examination (ρ = −0.62, p = 0.0001), Clinical Dementia Rating Scale sum of boxes (ρ = 0.79, p < 0.0001), baseline brain volume (ρ = −0.62, p = 0.0002), and whole-brain atrophy rate (ρ = 0.53, p = 0.01). Conclusions: Serum NfL concentration is increased in FAD prior to symptom onset and correlates with measures of disease stage and severity. Serum NfL may thus be a feasible biomarker of early AD-related neurodegeneration.

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  1. Nelson HE, Wilson JR. National Adult Reading Test (NART), 2nd ed. Windsor: NFER-Nelson; 1991.

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Metadata

Authors
Weston, P. S. J., Poole, T., Ryan, N. S., Nair, A., Liang, Y., Macpherson, K., Druyeh, R., Malone, I. B., Ahsan, R. L., Pemberton, H., Klimova, J., Mead, S., Blennow, K., Rossor, M. N., Schott, J. M., Zetterberg, H., & Fox, N. C.
Affiliations
  • London School of Hygiene & Tropical Medicine (GB)
  • From the Dementia Research Centre (P.S.J.W., T.P., N.S.R., A.N., Y.L., K.M., I.B.M., R.L.A., H.P., J.K., M.N.R., J.M.S., N.C.F.) and MRC Prion Unit (R.D., S.M.), Department of Neurodegenerative Diseases, UCL Institute of Neurology; Department of Medical Statistics (T.P.), London School of Hygiene &amp; Tropical Medicine, UK; and Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology (K.B., H.Z.), the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Corresponding author
Fox, Nick C.
Venue
Neurology
Published
2017-11-21
Volume
89
Issue
21
Pages
2167-2175
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
OpenAlex
W2766030065
Cited by
245
References
41
Citations by year
2026: 6 · 2025: 10 · 2024: 23 · 2023: 22 · 2022: 29 · 2021: 34 · 2020: 54 · 2019: 41 · 2018: 24 · 2017: 2
FWCI
24.49
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Neurology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • National Institute for Health and Care Research (NF-SI-0512-10033, NF-SI-0513-10134)
  • Medical Research Council (MR/L023784/2, MR/M003108/1, MR/L023784/1)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
serum neurofilament light, familial Alzheimer's disease, presymptomatic mutation carriers, PSEN1 mutations, APP mutations, brain atrophy rate, cognitive decline, disease stage, brain volume
MeSH terms
Adult, Alzheimer Disease, Cross-Sectional Studies, Family Health, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Mental Status Schedule, Middle Aged, Neuropsychological Tests, Amyloid beta-Protein Precursor, Neurofilament Proteins, Disease Progression, Neurodegenerative Diseases, Presenilin-1

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