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Serum neurofilament light in familial Alzheimer disease: A marker of early neurodegeneration
Open accessAbstract
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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“However, longitudinal analyses are largely missing and the importance of NfL as a molecular biomarker for the presymptomatic phase of neurodegenerative diseases remains unclear6,9,17.”
From Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease (2019) · cites this paper as [9]
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“Consistently, previous studies reported only non-significant or barely significant increases in absolute NfL in the blood in presymptomatic or even mildly cognitive impaired Alzheimer’s disease patients6,9,13.”
From Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease (2019) · cites this paper as [9]
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“Blood biomarkers for the presymptomatic phase of Alzheimer’s disease are largely lacking, although recent progress in the analysis of amyloid-β, tau, and neurofilament light chain (NfL) in the blood have been reported5–10.”
From Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease (2019) · cites this paper as [9]
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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 & 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.
- ORCID
- Venue
- Neurology
- Published
- 2017-11-21
- Volume
- 89
- Issue
- 21
- Pages
- 2167-2175
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC5696646
- 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
- hybrid
- doi.org
- 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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