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Article ; Online: Longitudinal serum neurofilament light kinetics in post-anoxic encephalopathy.

Disanto, Giulio / Villa, Michele / Maleska Maceski, Aleksandra / Prosperetti, Chiara / Gobbi, Claudio / Kuhle, Jens / Cassina, Tiziano / Agazzi, Pamela

Annals of clinical and translational neurology

2023 Volume 10, Issue 12, Page(s) 2407–2412

Abstract: Serum neurofilament light (sNfL) is a promising marker of outcome after cardiac arrest, but its kinetics are unclear. We prospectively measured sNfL concentrations in 62 patients at 0, 1, 3, 5, 7 and 10 days after cardiac arrest. Survivors and non- ... ...

Abstract	Serum neurofilament light (sNfL) is a promising marker of outcome after cardiac arrest, but its kinetics are unclear. We prospectively measured sNfL concentrations in 62 patients at 0, 1, 3, 5, 7 and 10 days after cardiac arrest. Survivors and non-survivors had similar sNfL at admission (14.2 [8.6-21.9] vs. 22.5 [14.2-46.9] pg/mL) but largely different at 24 h (16.4 [10.2-293] vs. 464.3 [151.8-1658.2], respectively). The AUC for sNfL concentrations predicting death was above 0.95 from Day 1 to 10 (highest on Day 3). Late sNfL measurements may exert prognostic value, especially when early samples are unavailable or prognosis remains unclear.
MeSH term(s)	Humans ; Biomarkers ; Intermediate Filaments ; Neurofilament Proteins ; Hypoxia, Brain ; Heart Arrest/complications
Chemical Substances	Biomarkers ; Neurofilament Proteins
Language	English
Publishing date	2023-09-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.51903
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Article ; Online: A Longitudinal Investigation of Blood Neurofilament Light Chain Levels in Chronic Cocaine Users.

Bavato, Francesco / Kexel, Ann-Kathrin / Kluwe-Schiavon, Bruno / Maceski, Aleksandra / Baumgartner, Markus R / Seifritz, Erich / Kuhle, Jens / Quednow, Boris B

Molecular neurobiology

2023 Volume 60, Issue 7, Page(s) 3935–3944

Abstract: The identification of a blood marker of brain pathology that is sensitive to substance-induced neurotoxicity and dynamically responds to longitudinal changes in substance intake would substantially improve clinical monitoring in the field of substance ... ...

Abstract	The identification of a blood marker of brain pathology that is sensitive to substance-induced neurotoxicity and dynamically responds to longitudinal changes in substance intake would substantially improve clinical monitoring in the field of substance use and addiction. Here, we explored the hypothesis that plasma levels of neurofilament light chain (NfL), a promising marker of neuroaxonal pathology, are elevated in chronic cocaine users and longitudinally associated with changes in cocaine use. Plasma NfL levels were determined using single molecule array (SIMOA) technology at baseline and at a 4-month follow-up. Substance use was subjectively assessed with an extensive interview and objectively measured via toxicological analysis of urine and 4-month hair samples. In a generalized linear model corrected for sex, age, and body mass index, NfL plasma levels were elevated in cocaine users (n=35) compared to stimulant-naïve healthy controls (n=35). A positive correlation between cocaine hair concentration and NfL levels was also found. Changes in cocaine hair concentration (group analysis of increasers vs. decreasers) over the 4-month interval predicted NfL levels at follow-up, indicating a rise in NfL with increased cocaine use and a reduction with decreased use. No associations between use or change of use of other substances (including the neurotoxic cocaine adulterant levamisole) and NfL levels were found. Our findings demonstrate that NfL is a sensitive marker for assessing cocaine-related neuroaxonal pathology, supporting the utility of blood NfL analysis in addiction research but also suggesting the detailed assessment of substance use in neurological studies and diagnostics.
MeSH term(s)	Humans ; Intermediate Filaments ; Neurofilament Proteins ; Cocaine-Related Disorders ; Biomarkers
Chemical Substances	Neurofilament Proteins ; Biomarkers
Language	English
Publishing date	2023-03-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-023-03327-6
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Article ; Online: Serum neurofilament light and white matter characteristics in the general population: a longitudinal analysis.

Hermesdorf, Marco / Wulms, Niklas / Maceski, Aleksandra / Leppert, David / Benkert, Pascal / Wiendl, Heinz / Kuhle, Jens / Berger, Klaus

GeroScience

2023 Volume 46, Issue 1, Page(s) 463–472

Abstract: Neurofilament light polypeptide (NfL) is a component of the neuronal cytoskeleton and particularly abundant in large-caliber axons. When axonal injury occurs, NfL is released and reaches the cerebrospinal fluid and the blood. Associations between NfL and ...

Abstract	Neurofilament light polypeptide (NfL) is a component of the neuronal cytoskeleton and particularly abundant in large-caliber axons. When axonal injury occurs, NfL is released and reaches the cerebrospinal fluid and the blood. Associations between NfL and white matter alterations have previously been observed in studies based on patients with neurological diseases. The current study aimed to explore the relationship between serum NfL (sNfL) and white matter characteristics in a population-based sample. The cross-sectional associations between sNfL as dependent variable, fractional anisotropy (FA), and white matter lesion (WML) volume were analyzed with linear regression models in 307 community-dwelling adults aged between 35 and 65 years. These analyses were repeated with additional adjustment for the potential confounders age, sex, and body mass index (BMI). Longitudinal associations over a mean follow-up of 5.39 years were analyzed with linear mixed models. The unadjusted cross-sectional models yielded significant associations between sNfL, WML volume, and FA, respectively. However, after the adjustment for confounders, these associations did not reach significance. In the longitudinal analyses, the findings corroborated the baseline findings showing no significant associations between sNfL and white matter macrostructure and microstructure beyond the effects of age. In synopsis with previous studies in patients with acute neurological diseases showing a significant association of sNfL with white matter changes beyond the effects of age, the present results based on a sample from the general population suggest the perspective that changes in sNfL reflect age-related effects that also manifest in altered white matter macrostructure and microstructure.
MeSH term(s)	Humans ; Aged ; White Matter/diagnostic imaging ; Brain/pathology ; Intermediate Filaments ; Cross-Sectional Studies ; Neurofilament Proteins ; Vascular Diseases/pathology
Chemical Substances	Neurofilament Proteins
Language	English
Publishing date	2023-06-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-023-00846-x
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Article: Polygenic risk for Alzheimer's disease is associated with neuroaxonal damage before onset of clinical symptoms.

Kagerer, Sonja M / Awasthi, Swapnil / Ripke, Stephan / Maceski, Aleksandra / Benkert, Pascal / Fall, Aïda B / Riederer, Peter / Fischer, Peter / Walitza, Susanne / Grünblatt, Edna / Kuhle, Jens / Unschuld, Paul G

Alzheimer's & dementia (Amsterdam, Netherlands)

2024 Volume 16, Issue 1, Page(s) e12504

Abstract: Introduction: Establishing valid diagnostic strategies is a precondition for successful therapeutic intervention in Alzheimer's disease (AD).: Methods: One hundred forty-four healthy 75-year-old participants from the Vienna-Transdanube-Aging ... ...

Abstract	Introduction: Establishing valid diagnostic strategies is a precondition for successful therapeutic intervention in Alzheimer's disease (AD). Methods: One hundred forty-four healthy 75-year-old participants from the Vienna-Transdanube-Aging longitudinal cohort study were tested for neuroaxonal damage by single molecular array (Simoa) plasma neurofilament light chain (NfL) levels at baseline, 30, 60, and 90 months, and onset of AD dementia. Individual risk for sporadic AD was estimated by continuous shrinkage polygenic risk score (PRS-CS, genome-wide association study). Results: Nineteen participants developed AD after a median of 60 months (interquartile range 30). In participants with AD, baseline NfL plasma levels correlated with PRS-CS ( Discussion: Our data suggest that polygenic risk for AD and plasma NfL closely interact years before onset of clinical symptoms. Peripheral NfL may serve as a diagnostic measure supporting early therapeutic intervention and secondary prevention in AD.
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2832898-X
ISSN	2352-8729
ISSN	2352-8729
DOI	10.1002/dad2.12504
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Article ; Online: Neurofilament light chain predicts future dementia risk in cerebral small vessel disease.

Egle, Marco / Loubiere, Laurence / Maceski, Aleksandra / Kuhle, Jens / Peters, Nils / Markus, Hugh S

Journal of neurology, neurosurgery, and psychiatry

2021

Abstract: Objectives: Serum neurofilament light chain (NfL) has been proposed as prognostic markers in neurogenerative disease. A cross-sectional study in cerebral small vessel disease (SVD) reported an association with cognition and disability. If NfL is to be ... ...

Abstract	Objectives: Serum neurofilament light chain (NfL) has been proposed as prognostic markers in neurogenerative disease. A cross-sectional study in cerebral small vessel disease (SVD) reported an association with cognition and disability. If NfL is to be used to predict outcome, studies are required to demonstrate baseline NfL predicts future dementia risk. Furthermore, if it is to be used as a surrogate marker in clinical trials, change in NfL over time periods typical of a clinical trial must be linked to clinical progression. In a longitudinal study of patients with lacunar stroke and confluent white matter hyperintensities, we determined whether both baseline, and change, in NfL levels were linked to changes in MRI markers, cognitive decline and dementia risk. Methods: Patients underwent MRI, cognitive testing and blood taking at baseline and annually for 3 years. Clinical and cognitive follow-up continued for 5 years. Results: NfL data were available for 113 subjects for baseline analysis, and 90 patients for the longitudinal analysis. Baseline NfL predicted cognitive decline (global cognition β Conclusions: Baseline NfL predicts changes in MRI markers, cognitive decline and dementia rate over a 5 years follow-up period in SVD, suggesting NfL may be a useful prognostic marker. However, change in NfL values was not detected, and therefore NfL may not be a useful surrogate marker in clinical trials in SVD.
Language	English
Publishing date	2021-02-08
Publishing country	England
Document type	Journal Article
ZDB-ID	3087-9
ISSN	1468-330X ; 0022-3050
ISSN (online)	1468-330X
ISSN	0022-3050
DOI	10.1136/jnnp-2020-325681
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Article ; Online: Dynamics of Inflammatory and Neurodegenerative Biomarkers after Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis.

Ruder, Josefine / Dinner, Gianna / Maceski, Aleksandra / Berenjeno-Correa, Ernesto / Müller, Antonia Maria / Jelcic, Ilijas / Kuhle, Jens / Martin, Roland

International journal of molecular sciences

2022 Volume 23, Issue 18

Abstract: Autologous hematopoietic stem cell transplantation (aHSCT) is a highly efficient treatment of multiple sclerosis (MS), and hence it likely normalizes pathological and/or enhances beneficial processes in MS. The disease pathomechanisms include ... ...

Abstract	Autologous hematopoietic stem cell transplantation (aHSCT) is a highly efficient treatment of multiple sclerosis (MS), and hence it likely normalizes pathological and/or enhances beneficial processes in MS. The disease pathomechanisms include neuroinflammation, glial cell activation and neuronal damage. We studied biomarkers that in part reflect these, like markers for neuroinflammation (C-X-C motif chemokine ligand (CXCL) 9, CXCL10, CXCL13, and chitinase 3-like 1 (CHI3L1)), glial perturbations (glial fibrillary acidic protein (GFAP) and in part CHI3L1), and neurodegeneration (neurofilament light chain (NfL)) by enzyme-linked immunosorbent assays (ELISA) and single-molecule array assay (SIMOA) in the serum and cerebrospinal fluid (CSF) of 32 MS patients that underwent aHSCT. We sampled before and at 1, 3, 6, 12, 24 and 36 months after aHSCT for serum, as well as before and 24 months after aHSCT for CSF. We found a strong increase of serum CXCL10, NfL and GFAP one month after the transplantation, which normalized one and two years post-aHSCT. CXCL10 was particularly increased in patients that experienced reactivation of cytomegalovirus (CMV) infection, but not those with Epstein-Barr virus (EBV) reactivation. Furthermore, patients with CMV reactivation showed increased Th1 phenotype in effector memory CD4+ T cells. Changes of the other serum markers were more subtle with a trend for an increase in serum CXCL9 early post-aHSCT. In CSF, GFAP levels were increased 24 months after aHSCT, which may indicate sustained astroglia activation 24 months post-aHSCT. Other CSF markers remained largely stable. We conclude that MS-related biomarkers indicate neurotoxicity early after aHSCT that normalizes after one year while astrocyte activation appears increased beyond that, and increased serum CXCL10 likely does not reflect inflammation within the central nervous system (CNS) but rather occurs in the context of CMV reactivation or other infections post-aHSCT.
MeSH term(s)	Biomarkers ; Chitinases ; Cytomegalovirus Infections ; Epstein-Barr Virus Infections ; Glial Fibrillary Acidic Protein ; Hematopoietic Stem Cell Transplantation/adverse effects ; Herpesvirus 4, Human ; Humans ; Ligands ; Multiple Sclerosis ; Transplantation, Autologous
Chemical Substances	Biomarkers ; Glial Fibrillary Acidic Protein ; Ligands ; Chitinases (EC 3.2.1.14)
Language	English
Publishing date	2022-09-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231810946
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Article ; Online: Longitudinal analyses of serum neurofilament light and associations with obesity indices and bioelectrical impedance parameters.

Hermesdorf, Marco / Leppert, David / Maceski, Aleksandra / Benkert, Pascal / Wellmann, Jürgen / Wiendl, Heinz / Kuhle, Jens / Berger, Klaus

Scientific reports

2022 Volume 12, Issue 1, Page(s) 15863

Abstract: Neurofilament light is a constituent of the neuronal cytoskeleton and released into the blood following neuro-axonal damage. It has previously been reported that NfL measured in blood serum is inversely related to body mass index. However, no reports ... ...

Abstract	Neurofilament light is a constituent of the neuronal cytoskeleton and released into the blood following neuro-axonal damage. It has previously been reported that NfL measured in blood serum is inversely related to body mass index. However, no reports exist with regard to body composition assessed using bioelectrical impedance analysis or other indicators of obesity beyond BMI. We analyzed the relationship between sNfL and body composition according to the three compartment model. Additionally, associations between sNfL, body shape index, waist-to-height ratio, and BMI were examined. The sample consisted of 769 participants assessed during the baseline examination and 693 participants examined in the course of the follow-up of the BiDirect Study. Associations between sNfL, BMI, BSI, and WtHR were separately analyzed using linear mixed models. Body compartments operationalized as fat mass, extracellular cell mass, and body cell mass were derived using BIA and the relationship with sNfL was analyzed with a linear mixed model. Lastly, we also analyzed the association between total body water and sNfL. We found significant inverse associations of sNfL with BMI and WtHR. The analysis of the three compartment model yielded significant inverse associations between sNfL, body cell mass and body fat mass, but not extracellular mass. Furthermore, total body water was also inversely related to sNfL. A potential mechanism could involve body cell mass and body fat mass as highly adaptive body constituents that either directly absorb sNfL, or promote the formation of new vasculature and thereby increase blood volume.
MeSH term(s)	Biomarkers ; Electric Impedance ; Humans ; Intermediate Filaments ; Neurofilament Proteins ; Obesity ; Serum
Chemical Substances	Biomarkers ; Neurofilament Proteins
Language	English
Publishing date	2022-09-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-20398-y
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Article ; Online: Serum neurofilament light chain as a reliable biomarker of hereditary transthyretin-related amyloidosis-A Swiss reference center experience.

Loser, Valentin / Benkert, Pascal / Vicino, Alex / Lim Dubois Ferriere, Pansy / Kuntzer, Thierry / Pasquier, Jérôme / Maceski, Aleksandra / Kuhle, Jens / Theaudin, Marie

Journal of the peripheral nervous system : JPNS

2022 Volume 28, Issue 1, Page(s) 86–97

Abstract: Hereditary transthyretin-related (hATTR) amyloidosis is a rare disease, causing a disabling and life-threatening axonal length-dependent polyneuropathy. Monitoring of disease progression and treatment response is difficult. We aimed to determine if serum ...

Abstract	Hereditary transthyretin-related (hATTR) amyloidosis is a rare disease, causing a disabling and life-threatening axonal length-dependent polyneuropathy. Monitoring of disease progression and treatment response is difficult. We aimed to determine if serum neurofilament light chain (sNfL) is a reliable and early biomarker of peripheral neuropathy in hATTR amyloidosis. We prospectively included 20 hATTR patients, 14 symptomatic and 6 asymptomatic. Patients were assessed at baseline and 1 year, including a full clinical examination with disease severity and functional scores, electrochemical skin conductance measurement with Sudoscan and nerve conduction studies, and sNfL level. hATTR patient sNfL were also compared with sNfL of 4532 healthy controls of a reference database by calculating age and BMI-adjusted Z scores. At baseline, median sNfL concentration was 3.6-fold higher in symptomatic than asymptomatic hATTR patients (P = .003), and this difference was also found in our under 60-years-old patients (P = .003). There was no significant difference of sNfL concentration between asymptomatic patients and healthy controls (Z-score of -0.29), but a significant difference between symptomatic patients and healthy controls (Z-score of 2.52). We found a significant correlation between sNfL levels and most clinical and electrophysiological disease severity scores, the strongest correlation being with the NIS score. sNfL seems to be a reliable biomarker of peripheral neuropathy severity in hATTR amyloidosis and can distinguish between asymptomatic and symptomatic patients. sNfL could also become a reliable biomarker to establish disease onset and treatment response.
MeSH term(s)	Humans ; Middle Aged ; Intermediate Filaments ; Prealbumin ; Switzerland ; Amyloid Neuropathies, Familial/diagnosis ; Biomarkers ; Neurofilament Proteins
Chemical Substances	Prealbumin ; Biomarkers ; Neurofilament Proteins
Language	English
Publishing date	2022-12-11
Publishing country	United States
Document type	Case Reports
ZDB-ID	1364009-4
ISSN	1529-8027 ; 1085-9489
ISSN (online)	1529-8027
ISSN	1085-9489
DOI	10.1111/jns.12524
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Article: A longitudinal investigation of blood neurofilament light chain levels in chronic cocaine users

Bavato, Francesco / Kexel, Ann-Kathrin / Kluwe-Schiavon, Bruno / Maceski, Aleksandra / Baumgartner, Markus R. / Seifritz, Erich / Kuhle, Jens / Quednow, Boris B.

Molecular Neurobiology

2023 Volume 60, Issue 7, Page(s) 3935–3944

Title translation	Eine Längsschnittuntersuchung des Neurofilament-Leichtkettenspiegels im Blut von chronischen Kokainkonsumenten
Abstract	The identification of a blood marker of brain pathology that is sensitive to substance-induced neurotoxicity and dynamically responds to longitudinal changes in substance intake would substantially improve clinical monitoring in the field of substance use and addiction. Here, we explored the hypothesis that plasma levels of neurofilament light chain (NfL), a promising marker of neuroaxonal pathology, are elevated in chronic cocaine users and longitudinally associated with changes in cocaine use. Plasma NfL levels were determined using single molecule array (SIMOA) technology at baseline and at a 4-month follow-up. Substance use was subjectively assessed with an extensive interview and objectively measured via toxicological analysis of urine and 4-month hair samples. In a generalized linear model corrected for sex, age, and body mass index, NfL plasma levels were elevated in cocaine users (n=35) compared to stimulant-naive healthy controls (n=35). A positive correlation between cocaine hair concentration and NfL levels was also found. Changes in cocaine hair concentration (group analysis of increasers vs. decreasers) over the 4-month interval predicted NfL levels at follow-up, indicating a rise in NfL with increased cocaine use and a reduction with decreased use. No associations between use or change of use of other substances (including the neurotoxic cocaine adulterant levamisole) and NfL levels were found. Our findings demonstrate that NfL is a sensitive marker for assessing cocaine-related neuroaxonal pathology, supporting the utility of blood NfL analysis in addiction research but also suggesting the detailed assessment of substance use in neurological studies and diagnostics.
Keywords	Blood Plasma ; Blutplasma ; Cocaine ; Drogenkonsum ; Drogensucht ; Drug Addiction ; Drug Usage ; Haar ; Hair ; Kokain ; Neurotoxicity ; Neurotoxizität ; Screening Tests ; Urin ; Urine
Language	English
Document type	Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-023-03327-6
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Article ; Online: New Perspectives of Multiplex Mass Spectrometry Blood Protein Quantification on Microsamples in Biological Monitoring of Elderly Patients.

Vialaret, Jérôme / Vignon, Margaux / Badiou, Stéphanie / Baptista, Gregory / Fichter, Laura / Dupuy, Anne-Marie / Maceski, Aleksandra Maleska / Fayolle, Martin / Brousse, Mehdi / Cristol, Jean-Paul / Jeandel, Claude / Hirtz, Christophe / Lehmann, Sylvain

International journal of molecular sciences

2023 Volume 24, Issue 8

Abstract: Blood microsampling combined with large panels of clinically relevant tests are of major interest for the development of home sampling and predictive medicine. The aim of the study was to demonstrate the practicality and medical utility of microsamples ... ...

Abstract	Blood microsampling combined with large panels of clinically relevant tests are of major interest for the development of home sampling and predictive medicine. The aim of the study was to demonstrate the practicality and medical utility of microsamples quantification using mass spectrometry (MS) in a clinical setting by comparing two types of microsamples for multiplex MS protein detection. In a clinical trial based on elderly population, we compared 2 µL of plasma to dried blood spot (DBS) with a clinical quantitative multiplex MS approach. The analysis of the microsamples allowed the quantification of 62 proteins with satisfactory analytical performances. A total of 48 proteins were significantly correlated between microsampling plasma and DBS (
MeSH term(s)	Aged ; Humans ; Activities of Daily Living ; Biological Monitoring ; Blood Proteins ; Specimen Handling ; Tandem Mass Spectrometry/methods
Chemical Substances	Blood Proteins
Language	English
Publishing date	2023-04-10
Publishing country	Switzerland
Document type	Clinical Trial ; Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24086989
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