Plasma neurofilament light chain: an early biomarker for hereditary ATTR amyloid polyneuropathy

Maia, Luı́s F.; Maceski, Aleksandra; Conceição, Isabel; Obici, Laura; Magalhães, Rui; Cortese, Andrea; Leppert, David; Merlini, Giampaolo; Kühle, Jens; Saraiva, Maria João

doi:10.1080/13506129.2019.1708716

Cited by 45 publications

(79 citation statements)

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“…These findings indicate that sNfL is a sensitive biomarker for the detection of PNP in an early disease stage, and correlates with severity of PNP. The results of our cohort of patients with diverse TTR genotypes are in line with a recent study of two independent cohorts of ATTR-V30Met patients [18] and a recent study involving diverse TTR genotypes [19].…”

Section: Discussionsupporting

confidence: 90%

“…This study demonstrates that sNfL levels are increased in patients with PNP due to AL amyloidosis, and confirms previous studies showing that sNfL levels are increased and correlate with severity of PNP in patients with PNP due to ATTRv amyloidosis [18,19]. This study indicates that sNfL is a useful biomarker for PNP diagnosis and severity, not only in ATTRv, but also in AL amyloidosis.…”

Section: Discussionsupporting

confidence: 90%

“…The positive relationship between NfL levels and age observed in individuals without PNP (healthy controls and TTRv carriers) has previously been reported [17,18]. We did not find an age-dependent increase in sNfL levels in patients with PNP.…”

Section: Discussionsupporting

confidence: 70%

“…However, the diagnostic value of sNfL as a biomarker for PNP in systemic amyloidosis has not been studied in detail. Two recent reports suggest that sNfL is increased in patients with ATTRv amyloidosis and PNP [18,19].…”

Section: Introductionmentioning

confidence: 95%

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Neurofilament light chain, a biomarker for polyneuropathy in systemic amyloidosis

Louwsma

Brunger

Bijzet

et al. 2020

Amyloid

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Objective: To study serum neurofilament light chain (sNfL) in amyloid light chain (AL) amyloidosis patients with and without polyneuropathy (PNP) and to corroborate previous observations that sNfL is increased in hereditary transthyretin-related (ATTRv) amyloidosis patients with PNP. Methods: sNfL levels were assessed retrospectively in patients with AL amyloidosis with and without PNP (AL/PNPþ and AL/PNP-, respectively), patients with ATTRv amyloidosis and PNP (ATTRv/PNPþ), asymptomatic transthyretin (TTR) gene mutation carriers (TTRv carriers) and healthy controls. Healthy controls (HC) were age-and sex-matched to both AL/PNP-(HC/AL) and TTRv carriers (HC/TTRv). The single-molecule array (Simoa) assay was used to assess sNfL levels. Results: sNfL levels were increased both in 10 AL/PNPþ patients (p < .001) and in 10 AL/PNP-patients (p < .005) compared to 10 HC/AL individuals. sNfL levels were higher in AL/PNPþ patients than in AL/ PNP-patients (p < .005). sNfL levels were also increased in 15 ATTRv/PNPþ patients, compared to both 15 HC/TTRv (p < .0001) and 15 TTRv carriers (p < .0001). ATTRv/PNPþ patients with progressive PNP (PND-score > I) had the highest sNfL levels compared to patients with early PNP (PND-score I) (p ¼ .05). sNfL levels did not differ between TTRv carriers and HC/TTRv individuals. In the group comprising all healthy controls and in the group of TTRv carriers, sNfL levels correlated with age. Conclusion: sNfL levels are increased in patients with PNP in both AL and ATTRv amyloidosis and are related to severity of PNP in ATTRv amyloidosis. sNfL is a promising biomarker to detect PNP, not only in ATTRv but also in AL amyloidosis.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

Neurofilament light chain, a biomarker for polyneuropathy in systemic amyloidosis

Louwsma

Brunger

Bijzet

et al. 2020

Amyloid

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“…Further studies of these proteins may help further elucidate the multisystem manifestations of ATTRv amyloidosis. These results are consistent with raised plasma NfL levels recently observed in patients with ATTRv amyloidosis compared with healthy controls 18,19. Collectively the findings demonstrate that patient proteome changes are detectable following treatment, as well as support the identification of proteins that have both the potential to serve as biomarkers and offer insights into ATTRv amyloidosis disease biology.Of highest clinical interest are the high plasma NfL levels detected in patients with ATTRv amyloidosis with polyneuropathy, and the subsequent decrease of these following patisiran treatment.…”

supporting

confidence: 88%

Neurofilament Light Chain as a Biomarker of Hereditary Transthyretin-Mediated Amyloidosis

et al. 2021

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ObjectiveTo identify changes in the proteome associated with onset and progression of ATTRv amyloidosis, we performed an observational, case-controlled study which compared proteomes of patients with ATTRv amyloidosis and healthy controls.MethodsPlasma levels of >1,000 proteins were measured in patients with ATTRv amyloidosis with polyneuropathy who received either placebo or patisiran in the APOLLO study and in healthy controls. The impact of patisiran on the time profile of each protein was determined by linear mixed model at 0, 9, and 18 months. Neurofilament light chain (NfL) was further assessed using an orthogonal quantitative approach.ResultsLevels of 66 proteins were significantly changed with patisiran vs placebo, with NfL change most significant (p < 10−20). Analysis of changes in protein levels demonstrated that the proteome of patisiran-treated patients trended toward healthy controls at 18 months. Healthy controls' NfL levels were 4-fold lower than in patients with ATTRv amyloidosis with polyneuropathy (16.3 vs 69.4 pg/mL, effect: −53.1 pg/mL, 95% CI [–60.5 to −45.9]). NfL levels at 18 months increased with placebo (99.5 vs 63.2 pg/mL, 36.3 pg/mL, [16.5–56.1]) and decreased with patisiran treatment (48.8 vs 72.1 pg/mL, −23.3 pg/mL, [–33.4 to −13.1]) from baseline. At 18 months, improvement in modified Neuropathy Impairment Score +7 following patisiran significantly correlated with reduced NfL (R = 0.43, [0.29–0.55]).ConclusionsFindings suggest NfL may serve as a biomarker of nerve damage and polyneuropathy in ATTRv amyloidosis, may enable earlier diagnosis of patients with ATTRv amyloidosis, and facilitate monitoring of disease progression.Classification of evidenceThis study provides Class III evidence that NfL levels may enable earlier diagnosis of polyneuropathy in patients with ATTRv amyloidosis and facilitate monitoring of disease progression.

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Types and Concentrations of Blood-Based Biomarkers in Adults With Peripheral Neuropathies

et al. 2022

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ImportancePeripheral neuropathies are common conditions and can result in numbness, paresthesia, motor deficits, and pain. There is increasing evidence for the use of biomarkers as clinical indicators of the presence, severity, and prognosis of nerve lesions; however, biomarker identification has largely been focused on disorders of the central nervous system, and less is known about their role in the peripheral nervous system.ObjectiveTo assess blood-based biomarker concentrations associated with nerve involvement in patients with peripheral neuropathy compared with control participants.Data SourcesOvid, MEDLINE, Embase, and CINAHL were searched from inception to September 23, 2021.Study SelectionObservational studies reporting on blood biomarkers in patients diagnosed with peripheral neuropathy were included. This review was preregistered on PROSPERO and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were abstracted by 1 investigator and independently reviewed by a second.Data Extraction and SynthesisData were meta-analyzed when at least 2 studies reported the same biomarker with comparable methodology. Fixed-effects models were used when only 2 studies were included; random-effects models were used when more than 2 studies were included.Main Outcomes and MeasuresThe outcome of interest was concentration of biomarkers.ResultsThis review included 36 studies reporting on 4414 participants, including 2113 control participants and 2301 patients with peripheral neuropathy with 13 distinct peripheral neuropathy diagnoses. Diabetic neuropathy was the most common neuropathy diagnosis (13 studies), followed by Charcot-Marie-Tooth disease (6 studies) and Guillain-Barre syndrome (6 studies). Overall, 16 different blood-based biomarkers associated with nerve involvement were evaluated. The most used were neurofilament light chain, S100B, brain-derived neurotrophic factor, and neuron-specific enolase. Patients with peripheral neuropathy demonstrated significantly higher levels of neurofilament light chain compared with controls (standardized mean difference [SMD], 0.93 [95% CI, 0.82 to 1.05]; P &lt; .001). There were no significant differences in levels of S100B (SMD, 1.10 [95% CI, −3.08 to 5.28]; P = .38), brain-derived neurotrophic factor (SMD, −0.52 [95% CI, −2.23 to 1.19]; P = .40), or neuron-specific enolase (SMD, −0.00 [95% CI, −1.99 to 1.98]; P = .10) in patients with peripheral neuropathy compared with control participants.Conclusions and RelevanceThe findings of this systematic review and meta-analysis support the use of neurofilament light chain as a blood-based measure associated with the presence of neuronal injury in patients with peripheral neuropathy.

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Plasma neurofilament light chain: an early biomarker for hereditary ATTR amyloid polyneuropathy

Cited by 45 publications

References 21 publications

Neurofilament light chain, a biomarker for polyneuropathy in systemic amyloidosis

Neurofilament light chain, a biomarker for polyneuropathy in systemic amyloidosis

Neurofilament Light Chain as a Biomarker of Hereditary Transthyretin-Mediated Amyloidosis

Types and Concentrations of Blood-Based Biomarkers in Adults With Peripheral Neuropathies

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