Plasma neurofilament light chain as prognostic marker of cognitive decline in neurodegenerative diseases, a clinical setting study DOI Creative Commons

Karl Götze,

Agathe Vrillon, Julien Dumurgier

et al.

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: Oct. 19, 2024

Analysis of selected research cohorts has highlighted an association between plasma neurofilament light (NfL) protein and cross-sectional cognitive impairment as well longitudinal decline. However, the findings have yielded inconsistent results regarding its possible application in clinical practice. Despite potential prognostic significance, role NfL daily practice with unselected patients suffering from remains largely unexplored. This retrospective, monocentric study enrolled 320 Alzheimer's disease ([AD], n = 158), dementia Lewy body ([DLB], 30), frontotemporal ([FTD], 32), non-neurodegenerative diseases ([NND], 59) or subjective decline ([SCD], 41). Plasma levels were measured at baseline on Simoa platform. AD, DLB, FTD also analyzed altogether a 'degenerative conditions' subgroup, whereas SCD NND grouped 'non-degenerative subgroup. We assessed relationship performance, including global cognition six specific domains. A subset 239 had follow-up mini-mental state examinations (MMSE) up to 60 months. Models adjusted age, education level, glomerular filtration rate mass index. In patients, negatively associated (β=-1.28 (-1.81 ; -0.75) P < 0.001), memory (β=-1.48 (-2.38 -0.59), language (β=-1.72(-2.49 -0.95) praxis (β=-2.02 (-2.91 -1.13) 0.001) executive functions (β=-0.81, 0.001). Across diagnosis, all but specifically AD (respectively β=-0.71(-1.21 -0.211), 0.005 β=-1.29 (-2.17 -0.42), 0.004), attention LBD (β=-0.81(-1.16 -0.002), 0.03). Linear mixed-effects models showed that predicted MMSE population (βPlasmaNfLxTime=-0.15 (-0.26 -0.04), 0.006), neurodegenerative condition subgroup (βPlasmaNfLxTime=-0.21 (-0.37 − 0.06), 0.007), not our cohort, was faster dementia, which corroborates data obtained cohorts. Yet, predictive accelerated individuals without neurodegeneration, suggesting use neurodegeneration-specific biomarker.

Language: Английский

Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington’s disease decades before clinical motor diagnosis DOI Creative Commons
Rachael I. Scahill, Mena Farag, Michael Murphy

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Language: Английский

Citations

5
Plasma and CSF neurofilament light chain distinguish neurodegenerative from primary psychiatric conditions in a clinical setting DOI Creative Commons
Dhamidhu Eratne, Matthew Kang, Courtney Lewis

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(11), P. 7989 - 8001

Published: Oct. 6, 2024

Abstract INTRODUCTION People with neurodegenerative disorders (ND) frequently face diagnostic delay and misdiagnosis. We investigated blood cerebrospinal fluid (CSF) neurofilament light chain (NfL) to distinguish ND from primary psychiatric (PPD), a common challenge in clinical settings. METHODS Plasma CSF NfL levels were measured compared between groups, adjusting for age, sex, weight. RESULTS A total of 337 participants included: 136 ND, 77 PPD, 124 Controls. was 2.5‐fold elevated PPD had strong performance (area under the curve, [AUC]: 0.86, 81%/85% specificity/sensitivity) that comparable (2‐fold elevated, AUC: 0.89, 95%/71% specificity/sensitivity). Diagnostic especially younger people (40– < 60 years). Additional findings cutoffs optimized sensitivity specificity, issues important future translation. CONCLUSIONS This study adds evidence simple blood‐based biomarker assist as screening test neurodegeneration distinction Highlights significantly higher versus PPD. showed performance, NfL, people, where challenges are greater. Further research is needed on analytical reference range factors, These support neurodegeneration.

Language: Английский

Citations

6
Evaluation of serum neurofilament light chain and glial fibrillary acidic protein in the diagnosis of Alzheimer’s disease DOI Creative Commons

Tangni Fang,

Yaqian Dai,

Xueyi Hu

et al.

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 30, 2024

Purpose This study aimed to evaluate the use of serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in diagnosis Alzheimer’s disease (AD) differential between AD mild cognitive impairment (MCI). Methods From September 2021 October 2022, we collected venous blood from patients healthy individuals who visited our hospital’s Neurology Department, isolated detect NfL GFAP using direct chemiluminescence. The results were analyzed one-way analysis variance (ANOVA) receiver operating characteristic (ROC) curves. Results Pairwise comparisons among three groups showed that compared with health checkup (HC) group, increased both MCI ( P &lt; 0.05, 0.01). There significant differences groups, level group was higher p 0.01), while there no difference NfL. Both levels can independently diagnose ROC curve had a diagnostic efficacy, an area under (AUC) 0.928. cut-off values two markers for &gt; 40.09 pg./mL &gt;31.40 pg./mL. Sensitivity specificity 59.6 76.2%, respectively, GFAP, they 90.4 82.1%, respectively. combined improved efficiency (AUC = 0.931, sensitivity 78.8%, 92.3%). value 46.05 Conclusion be used as biomarkers AD. Serum has better efficacy distinguish MCI. A improve specificity.

Language: Английский

Citations

5
Characterizing plasma and cerebrospinal fluid biomarkers relevant to neurodegeneration in captive olive baboons (Papio anubis) DOI Creative Commons
Sarah J. Neal Webb, Sriram Chitta, Elizabeth R. Magden

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0318173 - e0318173

Published: Feb. 13, 2025

Alzheimer’s disease and related dementias (ADRD) present a significant global burden that is only expected to grow in the future. As such, there need develop investigate biomarkers identify individuals at risk of developing ADRD with goal providing early interventions treatments. Non-human primate (NHP) models neurodegeneration opportunities examine such preclinical model ability control several confounding factors research humans. Baboons naturally ADRD-related neuropathologies humans also exhibit, including age-related tau amyloid deposition. However, our knowledge, are no data characterizing fluid relevant or baboons. We collected plasma (N = 139) cerebrospinal (CSF, N 44) from captive baboons ranging age 3–19 years old. characterized as function age, sex, rearing status using bead-based bioplex human assay (Thermo Fisher Scientific’s Neuroscience 18-Plex Human ProcartaPlex™ Panel). Fluid were more detectable CSF compared plasma. Additionally, while sex did not significantly predict baboons, predicted levels eight 12 detected assay. Linear regressions showed total tau, pTau181, NGF-beta, GFAP, NF-H, S100B higher older NGF-beta. Lastly, incidence co-occurrence multiple measured CSF, but These show exhibit age-dependent changes used for clinical screening, diagnosis, prognosis ADRD, thereby further demonstrating value aging and, possibly, ADRD.

Language: Английский

Citations

0
Serum neurofilament light chain as a potential biomarker in restless legs syndrome: a cross-sectional study DOI
Aysu Yetiş, Asuman Çelikbilek, Bilal İlanbey

et al.

Neurological Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 6

Published: Feb. 28, 2025

Neurofilament light chain (NfL) has emerged as a promising biomarker for several neurological diseases. Therefore, we investigated its serum levels and their association with disease characteristics, including duration, severity, medication use in patients restless legs syndrome (RLS). This cross-sectional prospective study included 71 RLS 70 healthy controls. were characterized based on use. NfL quantified using commercial enzyme-linked immunosorbent assay kits. No significant differences observed between controls (p > 0.05). Furthermore, the not significantly associated duration or severity These findings do support of RLS. Further large-scale studies are needed to evaluate role

Language: Английский

Citations

0
A genetic and proteomic comparison of key AD biomarkers across tissues DOI Creative Commons
Thomas W. Marsh, Daniel Western, Jigyasha Timsina

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(9), P. 6423 - 6440

Published: July 30, 2024

Abstract INTRODUCTION Plasma has been proposed as an alternative to cerebrospinal fluid (CSF) for measuring Alzheimer's disease (AD) biomarkers, but no studies have analyzed in detail which biofluid is more informative genetics of AD. METHOD Eleven proteins associated with AD (α‐synuclein, apolipoprotein E [apoE], CLU, GFAP, GRN, NfL, NRGN, SNAP‐25, TREM2, VILIP‐1, YKL‐40) were assessed plasma ( n = 2317) and CSF 3107). Both genome‐wide association study (GWAS) analyses performed each protein, followed by functional annotation. Additional characterization biomarker included calculation correlations predictive power. RESULTS Eighteen protein quantitative train loci (pQTLs) 10 16 pQTLs 9 identified. shared some genetic loci, levels between tissues correlated weakly. better compared plasma. DISCUSSION The present results indicate that than Highlights identification novel trait both (CSF). neurodegeneration‐related (AD). Neurofilament light (NfL), triggering receptor expressed on myeloid cells 2 (TREM2), chitinase‐3‐like 1 (YKL‐40) tend show relatively strong inter‐tissue associations. A signal the APOE ) region was identified, eQTL APOC1 .

Language: Английский

Citations

1
Prodromal Alzheimer’s Disease: Global Cognition, Cue Efficiency, and Cerebrospinal Fluid Neurofilament Light Values Predict Short-Term Conversion to Dementia DOI
Carlota Méndez‐del‐Barrio, Manuel Medina-Rodríguez,

Gonzalo Mendoza-Vázquez

et al.

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 101(3), P. 877 - 887

Published: Sept. 24, 2024

Background: Predicting which patients with prodromal AD (pAD) will imminently convert to dementia may be paramount in a memory clinical setting, especially potential disease-modifying therapies on the horizon. Objective: To explore practical tool for this prediction, combining cognitive tests and cerebrospinal fluid (CSF) biomarkers. Methods: We designed longitudinal prospective, observational, multicenter study, enrolling pAD. Inclusion criteria comprised complaints, Mini-Mental State Examination (MMSE) score of≥22, impairment as indicated by Free Cued Selective Reminding Test Immediate Recall (FCSRT + IR) and/or TMA-93, Clinical Dementia Rating-Global Score (CDR-GS) of 0.5, positive CSF Aβ42/Aβ40 ratio (<0.095, Euroimmun). The primary outcome was conversion (CDR-GS≥1) within first year follow-up, referred “short-term conversion”. A multiple regression logistic model adopted design “Predict Short-Term Conversion” (PSTC) score. Results: Between 2020 2022, 83 were recruited. median age 74, 49.4% being women. Twenty-five (30.1%) classified short-term converters. PSTC incorporated baseline scores MMSE ( ≤24 = 3, >24 0) FCSRT IR Total ≤14 4, >14 0), neurofilament light chains (NfLs) concentrations (β=0.001299). demonstrated an area under curve 0.78 (95% CI: 0.67-0.90, p < 0.001), cutoff value 5.14 presenting 76% sensitivity 80% specificity. Conclusions: score, comprising two relatively brief test NfLs concentrations, could useful predicting converters among diagnosed

Language: Английский

Citations

1
Neurofilament heavy phosphorylated epitopes as biomarkers in ageing and neurodegenerative disease DOI Open Access
Laura Paoli, Matthew Kirkcaldie, Anna E. King

et al.

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Abstract From the day we are born, nervous system is subject to insult, disease and degeneration. Aberrant phosphorylation states in neurofilaments, major intermediate filaments of neuronal cytoskeleton, accompany mediate many pathological processes degenerative disease. Neuronal damage, degeneration death can release these internal components extracellular space eventually cerebrospinal fluid blood. Sophisticated assay techniques increasingly able detect their presence at very low levels, increasing utility as biomarkers providing insights differential diagnosis for earliest stages Although a variety studies focus on single or small clusters neurofilament phosphorylated epitopes, this review offers wider perspective landscape heavy subunit, filament component both ageing image

Language: Английский

Citations

1
Biomarkers of Synaptic Degeneration in Alzheimer’s Disease DOI
Qian Cheng,

Yiou Fan,

Pengfei Zhang

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 102642 - 102642

Published: Dec. 1, 2024

Language: Английский

Citations

1
Prominent Perspective on Existing Biological Hallmarks of Alzheimer’s Disease DOI
Namrata Singh, Srishti Sharma, Kallol K. Ghosh

et al.

Current Topics in Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 24(13), P. 1120 - 1133

Published: April 9, 2024

Biomarkers are the most significant diagnosis tools tending towards unique approaches and solutions for prevention cure of Alzheimer's Disease (AD). The current report provides a clear perception concept various biomarkers their prominent features through analysis to provide possible solution inhibition events in AD. Scientists around world truly believe that crucial hallmarks can serve as critical early diagnosis, cure, prevention, well future medicine. awareness understanding such would puzzled mechanism this neuronal disorder. Some argued present article still an experimental phase they need undergo specific clinical trials before be considered treatment.

Language: Английский

Citations

0