Plasma Neurofilament Light Chain Predicts Cognitive Progression in Prodromal and Clinical Dementia with Lewy Bodies

Padovani, Alessandro; Imarisio, Alberto; Carrarini, Claudia; Russo, Mirella; Masciocchi, Stefano; Gipponi, Stefano; Cottini, Elisabetta; Aarsland, Dag; Zetterberg, Henrik; Ashton, Nicholas J.; Hye, Abdul; Bonanni, Laura; Padovani, Alessandro

doi:10.3233/jad-210342

Cited by 34 publications

(33 citation statements)

References 31 publications

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“…The absence of difference between patients with FTD and AD might be explained by the inclusion of early-stage FTD subjects in our sample (20). We con rmed the results of prior publications (5,7) showing that patients with LBD presented higher levels of plasma NfL than NC, but also lower levels than patients with AD, FTD or OND.…”

Section: Discussionsupporting

confidence: 86%

“…Plasma NfL (pNfL) was shown to re ect axonal damage in selected study cohorts of neurodegenerative disorders: Alzheimer's disease (AD) (3), frontotemporal dementia (FTD)(4-6), or Lewy body disease (LBD) (5,7), with good accuracy for the discrimination of neurodegenerative diseases from controls (7). However, in daily clinical practice, patients often report unspeci c cognitive complaints or clinical symptoms, leading to two unmet needs: 1/to easily differentiate neurodegenerative from non-neurodegenerative disorders (NND), 2/ to help the clinicians re ne early preliminary diagnoses, among neurodegenerative conditions.…”

Section: Introductionmentioning

confidence: 99%

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Plasma Neurofilament Light Chain in memory clinic practice: evidence from a real-life study

Götze

Vrillon

Bouaziz‐Amar

et al. 2022

Preprint

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OBJECTIVE: To explore plasma neurofilament light chain (NfL) as a biomarker for diagnosis and staging of cognitive impairment, in a large cohort with assessments performed in clinical practice. METHODS: Retrospective, cross-sectional, monocentric study, from a tertiary memory clinic. Patients underwent cerebrospinal fluid core Alzheimer’s disease (AD) biomarker evaluation using ELISA or Elecsys methods, and plasma NfL analysis using the single molecule array technology. The patients’ biomarker data were examined for associations with: i/cognitive status ii/presence of neurodegenerative disease and iii/diagnostic groups. Differences in NfL were tested using analysis of variance (ANOVA). RESULTS: Participants (N= 558, mean age= 69.2±8.8, 56.5% women) were diagnosed with AD (n=298, considering dementia and MCI stages), frontotemporal dementia (FTD, n=57), Lewy body disease (LBD, n=40, considering MCI and dementia stages), other neurodegenerative diseases (OND, n=53, e.g Supranuclear Palsy, Corticobasal degeneration), non-neurodegenerative cognitive impairment (NND, n=97, e.g vascular lesions, epilepsy or psychiatric disorders) or neurological controls (NC, n=53). Mean plasma NfL (log, pg/mL) levels were higher in neurodegenerative than non-neurodegenerative disorders (1.35±0.2 vs 1.16±0.23, p<0.001), higher in all diagnostic groups than in NC (1.06 ± 0.23) p<0.001), and associated with the stage of cognitive impairment (p<0.001). DISCUSSION: Plasma NfL may be considered as a clinical-decision support tool, to help distinguish neurodegenerative from non-neurodegenerative disorders.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Plasma Neurofilament Light Chain in memory clinic practice: evidence from a real-life study

Götze

Vrillon

Bouaziz‐Amar

et al. 2022

Preprint

Self Cite

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“…Plasma NfL levels in patients with DLB were about 2-fold higher than in healthy controls (55.3 vs. 25.7 pg/ml) and the elevations correlate with disease severity and plasma NfL is the best predictor of cognitive decline compared to age, sex and baseline severity variables over a follow-up of 2 years (Pilotto et al, 2021).…”

Section: Dementia With Lewy Bodiesmentioning

confidence: 84%

Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies

2021

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Biomarkers of neurodegeneration and neuronal injury have the potential to improve diagnostic accuracy, disease monitoring, prognosis, and measure treatment efficacy. Neurofilament proteins (NfPs) are well suited as biomarkers in these contexts because they are major neuron-specific components that maintain structural integrity and are sensitive to neurodegeneration and neuronal injury across a wide range of neurologic diseases. Low levels of NfPs are constantly released from neurons into the extracellular space and ultimately reach the cerebrospinal fluid (CSF) and blood under physiological conditions throughout normal brain development, maturation, and aging. NfP levels in CSF and blood rise above normal in response to neuronal injury and neurodegeneration independently of cause. NfPs in CSF measured by lumbar puncture are about 40-fold more concentrated than in blood in healthy individuals. New ultra-sensitive methods now allow minimally invasive measurement of these low levels of NfPs in serum or plasma to track disease onset and progression in neurological disorders or nervous system injury and assess responses to therapeutic interventions. Any of the five Nf subunits – neurofilament light chain (NfL), neurofilament medium chain (NfM), neurofilament heavy chain (NfH), alpha-internexin (INA) and peripherin (PRPH) may be altered in a given neuropathological condition. In familial and sporadic Alzheimer’s disease (AD), plasma NfL levels may rise as early as 22 years before clinical onset in familial AD and 10 years before sporadic AD. The major determinants of elevated levels of NfPs and degradation fragments in CSF and blood are the magnitude of damaged or degenerating axons of fiber tracks, the affected axon caliber sizes and the rate of release of NfP and fragments at different stages of a given neurological disease or condition directly or indirectly affecting central nervous system (CNS) and/or peripheral nervous system (PNS). NfPs are rapidly emerging as transformative blood biomarkers in neurology providing novel insights into a wide range of neurological diseases and advancing clinical trials. Here we summarize the current understanding of intracellular NfP physiology, pathophysiology and extracellular kinetics of NfPs in biofluids and review the value and limitations of NfPs and degradation fragments as biomarkers of neurodegeneration and neuronal injury.

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“…Nf-L is an axonal structural protein which is highly expressed in large cases as compared to controls, with some authors suggesting that the strong association between Nf-L and age in healthy controls may confound comparisons. [41][42][43][44][45] A meta-analysis of CSF Nf-L showed a slight increase in PD cases, which did not reach statistical significance. 46 If there is an elevation of Nf-L in PD, it is likely to be to a small extent and is unlikely to be helpful as an isolated measure in the early diagnosis of PD.…”

Section: Neurofil Ament LI G Ht (Nf-l)mentioning

confidence: 93%

Blood based biomarkers for movement disorders

Morris

2022

Acta Neuro Scandinavica

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Movement disorders have been carefully clinically defined, based on clinico‐pathological series; however there is often diagnostic and prognostic uncertainty, especially in early stage disease. Blood‐based biomarkers for Alzheimer's disease (AD), particularly p‐tau181 and p‐tau217, may be useful in the movement disorder clinic, especially in identifying corticobasal syndrome due to AD pathology and in identifying Parkinson's disease (PD) patients at high risk for the future development of dementia. Serum or plasma neurofilament light (NfL) may be useful in separating Parkinson's plus syndromes (progressive supranuclear palsy—PSP, multiple system atrophy – MSA, and corticobasal syndrome—CBS) from PD. NfL is also a prognostic biomarker, in that the level of baseline or cross‐sectional plasma/serum NfL is associated with a worse prognosis in PD and PSP. The development of protein aggregation assays in cerebrospinal fluid and multiplex assays which can measure 100 s‐1000s of proteins in blood will provide new tools and insights for movement disorders for clinicians and researchers. The challenge is in efficiently integrating these tools into clinical practice and multi‐modal approaches, where biomarkers are combined with clinical, genetic, and imaging data may guide the future use of these technologies.

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Plasma Neurofilament Light Chain Predicts Cognitive Progression in Prodromal and Clinical Dementia with Lewy Bodies

Cited by 34 publications

References 31 publications

Plasma Neurofilament Light Chain in memory clinic practice: evidence from a real-life study

Plasma Neurofilament Light Chain in memory clinic practice: evidence from a real-life study

Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies

Blood based biomarkers for movement disorders

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