ArticleNeurobiology of disease2022
Cerebrospinal fluid neurofilament light chain is a marker of aging and white matter damage.
Article in Neurobiology of disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Association between blood-based protein biomarkers and brain MRI in the Alzheimer's disease continuum: a systematic review.Journal of neurology · 2024Pooled it
- Effects of Binge Drinking and Alcohol Withdrawal on Serum Neurofilament Levels.Addiction biology · 2026Trial
- Biomarker advancements in cerebral small vessel disease: An overview.Neural regeneration research · 2026Article
- Relationships of CSF biomarkers to cortical atrophy in early-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Association of plasma biomarkers with amyloid and tau PET in pre-dementia stages.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Association of Plasma Placental Growth Factor with White Matter Hyperintensities in Alzheimer's Disease.Biomolecules · 2025Article
- A study on structural imaging changes and serum neurofilament light chain (NfL) levels in individuals with white matter hyperintensities, combining imaging techniques with biomarker analysis.IBRO neuroscience reports · 2025Article
- Risk factors and clinical significance of neurodegenerative co-pathologies in symptomatic cerebral small vessel disease.Journal of neurology · 2025Article
- Neurofilament Light Chain and Multiple Sclerosis: Building a Neurofoundational Model of Biomarkers and Diagnosis.Neurology international · 2025Article
- Associations of Cerebrospinal Fluid Orexin-A, Alzheimer Disease Biomarkers, and Cognitive Performance.Annals of clinical and translational neurology · 2025Article
- Safety, Tolerability and Pharmacokinetic-Pharmacodynamic Relationship of NX210c Peptide in Healthy Elderly Volunteers: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study.Neurology and therapy · 2025Article
- From Cell Architecture to Mitochondrial Signaling: Role of Intermediate Filaments in Health, Aging, and Disease.International journal of molecular sciences · 2025Review
- Targeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Neuronal and glial dysfunction, white matter hyperintensities and cognition in ageing and Alzheimer's disease.Brain communications · 2025Article
- Neurofilament Light Chain as a Biomarker of Global Cognition in Individuals With Possible Vascular Mild Cognitive Impairment.Journal of geriatric psychiatry and neurology · 2025Article
- Biomarker pathway heterogeneity of amyloid-positive individuals.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Characterization of white matter hyperintensities in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Brain Expression Levels of Commonly Measured Blood Biomarkers of Neurological Damage Differ with Respect to Sex, Race, and Age.Neuroscience · 2024Article
- Benchmarking of a multi-biomarker low-volume panel for Alzheimer's Disease and related dementia research.medRxiv : the preprint server for health sciences · 2024Article
- Blood biomarkers of neurodegeneration associate differently with amyloid deposition, medial temporal atrophy, and cerebrovascular changes in APOE ε4-enriched cognitively unimpaired elderly.Alzheimer's research & therapy · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCerebrospinal fluid (CSF) neurofilament light chain (NfL) reflects neuro-axonal damage and is increasingly used to evaluate disease progression across neurological conditions including Alzheimer disease (AD). However, it is unknown how NfL relates to specific types of brain tissue. We sought to determine whether CSF NfL is more strongly associated with total gray matter, white matter, or white matter hyperintensity (WMH) volume, and to quantify the relative importance of brain tissue volume, age, and AD marker status (i.e., APOE genotype, brain amyloidosis, tauopathy, and cognitive status) in predicting CSF NfL.
methods419 participants (Clinical Dementia Rating [CDR] Scale > 0, N = 71) had CSF, magnetic resonance imaging (MRI), and neuropsychological data. A subset had amyloid positron emission tomography (PET) and tau PET. Pearson correlation analysis was used to determine the association between CSF NfL and age. Multiple regression was used to determine which brain volume (i.e., gray, white, or WMH volume) most strongly associated with CSF NfL. Stepwise regression and dominance analyses were used to determine the individual contributions and relative importance of brain volume, age, and AD marker status in predicting CSF NfL.
resultsCSF NfL increased with age (r = 0.59, p < 0.001). Elevated CSF NfL was associated with greater total WMH volume (p < 0.001), but not gray or white matter volume (p's > 0.05) when considered simultaneously. Age and WMH volume were consistently more important (i.e., have greater R
conclusionsCSF NfL is a non-specific marker of aging and white matter integrity with limited sensitivity to specific markers of AD. CSF NfL likely reflects processes associated with cerebrovascular disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.