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1.
J Alzheimers Dis ; 91(1): 291-303, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36617786

RESUMO

BACKGROUND: Most research on cerebrospinal fluid (CSF) neurofilament light protein (NfL) as a marker for neurodegeneration and neurogranin (Ng) for synaptic dysfunction has largely focused on clinical cohorts rather than population-based samples. OBJECTIVE: We hypothesized that increased CSF levels of NfL and Ng are associated with subtle cognitive deficits in cognitively unimpaired (CU) older adults. METHODS: The sample was derived from the Gothenburg H70 Birth Cohort Studies and comprised 258 CU 70-year-olds, with a Clinical Dementia Rating score of zero. All participants underwent extensive cognitive testing. CSF levels of NfL and Ng, as well as amyloid ß1 - 42, total tau, and phosphorylated tau, were measured. RESULTS: Participants with high CSF NfL performed worse in one memory-based test (Immediate recall, p = 0.013) and a language test (FAS, p = 0.016). Individuals with high CSF Ng performed worse on the memory-based test Supra Span (p = 0.035). When stratified according to CSF tau and Aß42 concentrations, participants with high NfL and increased tau performed worse on a memory test than participants normal tau concentrations (Delayed recall, p = 0.003). In participants with high NfL, those with pathologic Aß42 concentrations performed worse on the Delayed recall memory (p = 0.044). In the high Ng group, participants with pathological Aß42 concentrations had lower MMSE scores (p = 0.027). However, in regression analysis we found no linear correlations between CSF NfL or CSF Ng in relation to cognitive tests when controlled for important co-variates. CONCLUSION: Markers of neurodegeneration and synaptic pathology might be associated with subtle signs of cognitive decline in a population-based sample of 70-year-olds.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/patologia , Neurogranina/líquido cefalorraquidiano , Estudos Transversais , Proteínas tau/líquido cefalorraquidiano , Filamentos Intermediários , Cobre , Biomarcadores/líquido cefalorraquidiano , Cognição , Disfunção Cognitiva/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Proteínas de Neurofilamentos/líquido cefalorraquidiano
2.
Fluids Barriers CNS ; 20(1): 3, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631830

RESUMO

BACKGROUND: Impaired cerebrospinal fluid (CSF) homeostasis is central to the pathogenesis of idiopathic intracranial hypertension (IIH), although the precise mechanisms involved are still not completely understood. The aim of the current study was to assess the CSF/serum ratio of neurofilament light chain levels (QNfL) as a potential indicator of functional CSF outflow obstruction in IIH patients. METHODS: NfL levels were measured by single molecule array in CSF and serum samples of 87 IIH patients and in three control groups, consisting of 52 multiple sclerosis (MS) patients with an acute relapse, 21 patients with an axonal polyneuropathy (PNP), and 41 neurologically healthy controls (HC). QNfL was calculated as the ratio of CSF and serum NfL levels. Similarly, we also assessed the CSF/serum ratio of glial fibrillary acidic protein (QGFAP) levels to validate the QNfL data. Routine CSF parameters including the CSF/serum albumin ratio (QAlb) were determined in all groups. Lumbar puncture opening pressure of IIH patients was measured by manometry. RESULTS: CSF-NfL levels (r = 0.29, p = 0.008) and QNfL (0.40, p = 0.0009), but not serum NfL (S-NfL) levels, were associated with lumbar puncture opening pressure in IIH patients. CSF-NfL levels were increased in IIH patients, MS patients, and PNP patients, whereas sNfL levels were normal in IIH, but elevated in MS and PNP. Remarkably, QNfL (p < 0.0001) as well as QGFAP (p < 0.01) were only increased in IIH patients. QNfL was positively correlated with CSF-NfL levels (r = 0.51, p = 0.0012) and negatively correlated with S-NfL levels (r = - 0.51, p = 0.0012) in HC, while it was only positively associated with CSF-NfL levels in IIH patients (r = 0.71, p < 0.0001). An increase in blood-CSF barrier permeability assessed by QAlb did not lead to a decrease in QNfL in any cohort. CONCLUSIONS: The observed elevation of QNfL in IIH patients, which was associated with lumbar puncture opening pressure, indicates a reduced NfL transition from the CSF to serum compartment. This supports the hypothesis of a pressure-dependent CSF outflow obstruction to be critically involved in IIH pathogenesis.


Assuntos
Esclerose Múltipla , Pseudotumor Cerebral , Humanos , Filamentos Intermediários , Esclerose Múltipla/líquido cefalorraquidiano , Punção Espinal , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano
3.
Int J Mol Sci ; 24(2)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36674698

RESUMO

For a long time, Substance Use Disorders (SUDs) were not considered a component in the etiology of dementia. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders introduced substance-induced neurocognitive disorders, incorporating this notion to clinical practice. However, detection and monitoring of neurodegenerative processes in SUD patients remain a major clinical challenge, especially when early diagnosis is required. In the present study, we aimed to investigate new potential biomarkers of neurodegeneration that could predict cognitive impairment in SUD patients: the circulating concentrations of Neurofilament Light chain protein (NfL) and Brain-Derived Neurotrophic Factor (BDNF). Sixty SUD patients were compared with twenty-seven dementia patients and forty healthy controls. SUD patients were recruited and assessed using the Psychiatric Research Interview for Substance and Mental (PRISM) and a battery of neuropsychological tests, including the Montreal Cognitive Assessment test for evaluation of cognitive impairment. When compared to healthy control subjects, SUD patients showed increases in plasma NfL concentrations and NfL/BDNF ratio, as well as reduced plasma BDNF levels. These changes were remarkable in SUD patients with moderate-severe cognitive impairment, being comparable to those observed in dementia patients. NfL concentrations correlated with executive function and memory cognition in SUD patients. The parameters "age", "NfL/BDNF ratio", "first time alcohol use", "age of onset of alcohol use disorder", and "length of alcohol use disorder diagnosis" were able to stratify our SUD sample into patients with cognitive impairment from those without cognitive dysfunction with great specificity and sensibility. In conclusion, we propose the combined use of NfL and BDNF (NfL/BDNF ratio) to monitor substance-induced neurocognitive disorder.


Assuntos
Alcoolismo , Doença de Alzheimer , Disfunção Cognitiva , Demência , Humanos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Alcoolismo/complicações , Alcoolismo/diagnóstico , Alcoolismo/metabolismo , Filamentos Intermediários/metabolismo , Proteínas de Neurofilamentos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Demência/metabolismo , Biomarcadores/metabolismo , Doença de Alzheimer/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-36543540

RESUMO

BACKGROUND AND OBJECTIVES: The specificity of novel blood biomarkers for multiple sclerosis (MS)-related neurodegeneration is unclear because neurodegeneration also occurs during normal aging. To understand which aspects of neurodegeneration the serum biomarkers neurofilament light (sNfL), serum glial fibrillary acidic protein (sGFAP), and serum contactin-1 (sCNTN1) reflect, we here explore their cross-sectional association with disability outcome measures and MRI volumes in a unique cohort of people with MS (PwMS) of the same age. METHODS: sNfL, sGFAP (both singe-molecule array technology) and sCNTN1 (Luminex) were measured in serum samples of 288 PwMS and 125 healthy controls (HCs) of the Project Y cohort, a population-based cross-sectional study of PwMS born in the Netherlands in 1966 and age-matched HC. RESULTS: sNfL (9.83 pg/mL [interquartile range {IQR}: 7.8-12.0]) and sGFAP (63.7 pg/mL [IQR: 48.5-84.5]) were higher in PwMS compared with HC (sNfL: 8.8 pg/mL [IQR: 7.0-10.5]; sGFAP: 51.7 pg/mL [IQR: 40.1-68.3]) (p < 0.001), whereas contactin-1 (7,461.3 pg/mL [IQR: 5,951.8-9,488.6]) did not significantly differ between PwMS compared with HC (7,891.2 pg/mL [IQR: 6,120.0-10,265.8]) (p = 0.068). sNfL and sGFAP levels were 1.2-fold higher in secondary progressive patients (SPMS) compared with relapsing remitting patients (p = 0.009 and p = 0.043). Stratified by MS subtype, no relations were seen for CNTN1, whereas sNfL and sGFAP correlated with the Expanded Disability Status Scale (ρ = 0.43 and ρ = 0.39), Nine-Hole Peg Test, Timed 25-Foot Walk Test, and Symbol Digit Modalities Test (average ρ = 0.38) only in patients with SPMS. Parallel to these clinical findings, correlations were only found for sNfL and sGFAP with MRI volumes. The strongest correlations were observed between sNfL and thalamic volume (ρ = -0.52) and between sGFAP with deep gray matter volume (ρ = - 0.56) in primary progressive patients. DISCUSSION: In our cohort of patients of the same age, we report consistent correlations of sNfL and sGFAP with a range of metrics, especially in progressive MS, whereas contactin-1 was not related to clinical or MRI measures. This demonstrates the potential of sNfL and sGFAP as complementary biomarkers of neurodegeneration, reflected by disability, in progressive MS.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico por imagem , Estudos Transversais , Proteínas de Neurofilamentos , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Biomarcadores , Contactinas
6.
Artigo em Inglês | MEDLINE | ID: mdl-36376097

RESUMO

BACKGROUND AND OBJECTIVES: Neurodegeneration and astrocytic activation are pathologic hallmarks of progressive multiple sclerosis (MS) and can be quantified by serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). We investigated sNfL and sGFAP as tools for stratifying patients with progressive MS based on progression and disease activity status. METHODS: We leveraged our Comprehensive Longitudinal Investigation of MS at the Brigham and Women's Hospital (CLIMB) natural history study, which includes clinical, MRI data and serum samples collected over more than 20 years. We included patients with MS with a confirmed Expanded Disability Status Scale (EDSS) score ≥3 that corresponds with our classifier for patients at high risk of underlying progressive pathology. We analyzed sNfL and sGFAP within 6 months from the confirmed EDSS score ≥3 corresponding with our baseline visit. Patients who further developed 6-month confirmed disability progression (6mCDP) were classified as progressors. We further stratified our patients into active/nonactive based on new brain/spinal cord lesions or relapses in the 2 years before baseline or during follow-up. Statistical analysis on log-transformed sGFAP/sNfL assessed the baseline association with demographic, clinical, and MRI features and associations with future disability. RESULTS: We included 257 patients with MS who had an average EDSS score of 4.0 and a median follow-up after baseline of 7.6 years. sNfL was higher in patients with disease activity in the 2 years before baseline (adjusted ß = 1.21; 95% CI 1.04-1.42; p = 0.016), during the first 2 years of follow-up (adjusted ß = 1.17; 95% CI = 1.01-1.36; p = 0.042). sGFAP was not increased in the presence of disease activity. Higher sGFAP levels, but not sNfL levels, were associated with higher risk of 6mCDP (adjusted hazard ratio [HR] = 1.71; 95% CI = 1.19-2.45; p = 0.004). The association was stronger in patients with low sNfL (adjusted HR = 2.44; 95% CI 1.32-4.52; p = 0.005) and patients who were nonactive in the 2 years prior or after the sample. DISCUSSION: Higher levels of sGFAP correlated with subsequent progression, particularly in nonactive patients, whereas sNfL reflected acute disease activity in patients with MS at high risk of underlying progressive pathology. Thus, sGFAP and sNfL levels may be used to stratify patients with progressive MS for clinical research studies and clinical trials and may inform clinical care.


Assuntos
Proteína Glial Fibrilar Ácida , Esclerose Múltipla Crônica Progressiva , Proteínas de Neurofilamentos , Humanos , Biomarcadores/sangue , Proteína Glial Fibrilar Ácida/sangue , Imageamento por Ressonância Magnética , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Progressão da Doença , Proteínas de Neurofilamentos/sangue
9.
Int J Mol Sci ; 23(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36362248

RESUMO

In patients with slowly progressive spastic paraparesis, the differential diagnosis of primary progressive multiple sclerosis (PPMS) and hereditary spastic paraplegia (HSP) can be challenging. Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising fluid biomarkers to support the diagnostic workup. Serum NfL is a marker of neuroaxonal decay sensitive to temporal changes, while elevated sGFAP levels may reflect astrocytal involvement in PPMS. We assessed sNfL and sGFAP levels in 25 patients with PPMS, 25 patients with SPG4 (the most common type of HSP) and 60 controls, using the highly sensitive single-molecule array (Simoa) platform. Patients were matched in age, sex, age at onset, disease duration and disease severity. Serum NfL levels were significantly increased in PPMS compared to SPG4 (p = 0.041, partial η² = 0.088), and there was a trend toward relatively higher sGFAP levels in PPMS (p = 0.097). However, due to overlapping biomarker values in both groups, we did not find sNfL and sGFAP to be useful as differential biomarkers in our cohort. The temporal dynamics indicate sNfL and sGFAP levels are most markedly elevated in PPMS in earlier disease stages, supporting their investigation in this group most in need of a diagnostic biomarker.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Paraplegia Espástica Hereditária , Humanos , Proteína Glial Fibrilar Ácida , Filamentos Intermediários , Esclerose Múltipla/diagnóstico , Paraplegia Espástica Hereditária/diagnóstico , Proteínas de Neurofilamentos , Biomarcadores
10.
Eur Rev Med Pharmacol Sci ; 26(19): 6928-6934, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36263572

RESUMO

OBJECTIVE: Mild traumatic brain injury (mTBI) cases with a normal CT scanning account for the vast majority of all TBI patients. The aim of this study was to investigate the course of serum Phosphorylated Neurofilament Heavy Chain (pNF-H) levels in the first six hours after trauma in rats in experimental mTBI. MATERIALS AND METHODS: In this experimental animal study, 32 female Sprague-Dawley rats were enrolled equally (n=8) into 3 experimental groups and 1 control group. In experimental groups, animals were exposed to a mTBI with a free fall of 50-gram metal disc from a height of 80 cm. We compared serum pNF-H levels at the 2nd, 4th, and 6th hours after traumatic brain injury in the experimental groups with the control group. RESULTS: Serum pNF-H levels at the 2nd and 4th hours after traumatic brain injury were statistically significantly higher than the control group. Serum pNF-H levels gradually decreased at the 4th and 6th hours compared to the 2nd hour and decreased to a similar level to the control group at the 6th hour after injury. CONCLUSIONS: A high serum pNF-H value, could be used in the diagnosis and management of mTBI patients.


Assuntos
Concussão Encefálica , Lesões Encefálicas Traumáticas , Animais , Ratos , Feminino , Proteínas de Neurofilamentos , Ratos Sprague-Dawley , Biomarcadores , Lesões Encefálicas Traumáticas/diagnóstico
11.
Neurobiol Aging ; 120: 177-188, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36209638

RESUMO

Pathological biomarkers of dementia and Alzheimer's disease (AD) change decades before clinical symptoms. Common sensory and motor changes in aging adults may be early markers of neurodegeneration. We investigated if midlife sensory and motor functions in Beaver Dam Offspring Study (BOSS) participants (N = 1529) were associated with longitudinal changes in blood-based biomarkers of neurodegeneration (neurofilament light chain (NfL); total tau (TTau)) and AD (amyloid beta (Aß)). Mixed-effects models with baseline sensory and motor function as determinants and 10-year biomarker change as outcome were used. Participants with hearing impairment and worse motor function (among women) showed faster increases in NfL level over time (0.8% per year; 0.3% per year, respectively). There were no significant associations with TTau or Aß. We found consistent relationships between worse baseline hearing and motor function with a faster increase in neurodegeneration, specifically serum NfL level. Future studies with longer follow-up should determine if sensory and motor changes are more reflective of general neurodegeneration than AD-specific pathology and whether sensory and motor tests may be useful screening tools for neurodegeneration risk.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Feminino , Humanos , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Biomarcadores , Proteínas de Neurofilamentos , Proteínas tau , Doenças Neurodegenerativas/patologia , Sensação , Pessoa de Meia-Idade , Destreza Motora
12.
J Neuroinflammation ; 19(1): 252, 2022 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-36210459

RESUMO

BACKGROUND: Despite widespread searches, there are currently no validated biofluid markers for the detection of subclinical neuroinflammation in multiple sclerosis (MS). The dynamic nature of human metabolism in response to changes in homeostasis, as measured by metabolomics, may allow early identification of clinically silent neuroinflammation. Using the delayed-type hypersensitivity (DTH) MS rat model, we investigated the serum and cerebrospinal fluid (CSF) metabolomics profiles and neurofilament-light chain (NfL) levels, as a putative marker of neuroaxonal damage, arising from focal, clinically silent neuroinflammatory brain lesions and their discriminatory abilities to distinguish DTH animals from controls. METHODS: 1H nuclear magnetic resonance (NMR) spectroscopy metabolomics and NfL measurements were performed on serum and CSF at days 12, 28 and 60 after DTH lesion initiation. Supervised multivariate analyses were used to determine metabolomics differences between DTH animals and controls. Immunohistochemistry was used to assess the extent of neuroinflammation and tissue damage. RESULTS: Serum and CSF metabolomics perturbations were detectable in DTH animals (vs. controls) at all time points, with the greatest change occurring at the earliest time point (day 12) when the neuroinflammatory response was most intense (mean predictive accuracy [SD]-serum: 80.6 [10.7]%, p < 0.0001; CSF: 69.3 [13.5]%, p < 0.0001). The top discriminatory metabolites at day 12 (serum: allantoin, cytidine; CSF: glutamine, glucose) were all reduced in DTH animals compared to controls, and correlated with histological markers of neuroinflammation, particularly astrogliosis (Pearson coefficient, r-allantoin: r = - 0.562, p = 0.004; glutamine: r = - 0.528, p = 0.008). Serum and CSF NfL levels did not distinguish DTH animals from controls at day 12, rather, significant differences were observed at day 28 (mean [SEM]-serum: 38.5 [4.8] vs. 17.4 [2.6] pg/mL, p = 0.002; CSF: 1312.0 [379.1] vs. 475.8 [74.7] pg/mL, p = 0.027). Neither serum nor CSF NfL levels correlated with markers of neuroinflammation; serum NfL did, however, correlate strongly with axonal loss (r = 0.641, p = 0.001), but CSF NfL did not (p = 0.137). CONCLUSIONS: While NfL levels were elevated later in the pathogenesis of the DTH lesion, serum and CSF metabolomics were able to detect early, clinically silent neuroinflammation and are likely to present sensitive biomarkers for the assessment of subclinical disease activity in patients.


Assuntos
Esclerose Múltipla , Alantoína , Animais , Biomarcadores , Citidina , Modelos Animais de Doenças , Glucose , Glutamina , Humanos , Filamentos Intermediários , Esclerose Múltipla/líquido cefalorraquidiano , Proteínas de Neurofilamentos , Ratos
13.
Dis Markers ; 2022: 3880687, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212178

RESUMO

Objective: This study was to investigate the mechanism of action of polycaprolactone/gelatin (PCL/GE) composite fiber scaffold with nerve growth factor (NGF) in the recovery of spinal cord injury (SCI). Methods: Sixty female Sprague-Dawley (SD) rats were randomly assigned to the negative control group, the positive control group, the PCL/GE scaffold group, and the collagen-binding structural domain nerve growth factor (CBD-NGF)/PCL/GE scaffold group, with 15 rats in each group. Spinal cord transection was used to establish SCI models in rats. The negative control group received sham surgery, while the other three groups were given spinal cord transection at the tenth thoracic vertebra (T10) segment. The rats in the PCL/GE scaffold group were implanted with a 4 mm PCL/GE composite fiber scaffold, and those in the CBD-NGF/PCL/GE scaffold group were implanted with a CBD-NGF/PCL/GE composite fiber scaffold. The Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to evaluate the locomotor ability of the hind limbs of the rats, and the amplitude and latency of motor evoked potentials (MEP) were recorded by neurophysiological testing at 12 w postoperatively. The levels of growth-associated protein 43 (GAP43) and neurofilament protein 200 (NF200) in the spinal cord tissue of the injury site were determined using Western Blot at 12 w after surgery. Spinal cord tissues of 2 cm within the injury site, the thoracic segment above the injury site, and the lumbar segment below the injury site were collected from the measurement of axonal transport using fluorescent retrograde tracer fluorogold, and the integrated absorbance (IA) values of FC-positive cells were calculated. Results: After treatment, the negative control rats showed normal locomotion function of the hind limb with the highest BBB scores, while the positive control rats had the lowest BBB scores and showed paraplegia. The scaffold groups exhibited better locomotion function of the hind limb and higher BBB scores than the positive controls, with greater improvement observed in the CBD-NGF/PCL/GE scaffold group (P < 0.05). Compared with the positive controls, the PCL/GE scaffold group and CBD-NGF/PCL/GE scaffold group exhibited significantly shorter latency and increased amplitude of MEP, with more significant changes observed in the CBD-NGF/PCL/GE scaffold group (P < 0.05). Compared with the positive control group, the GAP43 and NF200 levels of spinal cord tissue were significantly elevated in both the PCL/GE scaffold group and the CBD-NGF/PCL/GE scaffold group, and the changes were more pronounced in the CBD-NGF/PCL/GE scaffold group (P < 0.05). The differences in the IA values of FC-positive cells in the spinal cord tissue of the lumbar segment below the injury site among the four groups did not come up to the statistical standard (P > 0.05). Compared with the positive control group, the FC-positive cell IA values of spinal cord tissue in the thoracic segment above the injury area were markedly increased in the PCL/GE scaffold group and the CBD-NGF/PCL/GE scaffold group, and the alterations were more significant in the CBD-NGF/PCL/GE scaffold group (P < 0.05). Conclusion: PCL/GE composite fiber scaffold with NGF significantly improves motor and neurological functions in the hind limbs of SCI rats and promotes the recovery of axonal transport, and the mechanism may be associated with the upregulation of GAP43 and NF200 levels in spinal cord injury site tissues.


Assuntos
Gelatina , Traumatismos da Medula Espinal , Animais , Colágeno , Feminino , Proteína GAP-43 , Fator de Crescimento Neural , Proteínas de Neurofilamentos , Poliésteres , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/terapia
14.
J Neurol Sci ; 442: 120439, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36201960

RESUMO

BACKGROUND: Distinguishing behavioural variant frontotemporal dementia (bvFTD) from non-neurodegenerative 'non-progressor' mimics of frontal lobe dysfunction, can be one of the most challenging clinical dilemmas. A biomarker of neuronal injury, neurofilament light chain (NfL), could reduce misdiagnosis and delay. METHODS: Cerebrospinal fluid (CSF) NfL, amyloid beta 1-42 (AB42), total and phosphorylated tau (T-tau, P-tau) levels were examined in patients with an initial diagnosis of bvFTD. Based on follow-up information, patients were categorised as Progressors or Non-Progressors: further subtyped into Non-Progressor Revised (non-neurological/neurodegenerative final diagnosis), and Non-Progressor Static (static deficits, not fully explained by non-neurological/neurodegenerative causes). RESULTS: Forty-three patients were included: 20 Progressors, 23 Non-Progressors (15 Non-Progressor Revised, 8 Non-Progressor Static), and 20 controls. NfL concentrations were lower in Non-Progressors (Non-Progressors Mean, M = 554 pg/mL, 95%CI:[461, 675], Non-Progressor Revised M = 459 pg/mL, 95%CI:[385, 539], and Non-Progressor Static M = 730 pg/mL, 95%CI:[516, 940]), compared to Progressors (M = 2397 pg/mL, 95%CI:[1607, 3332]). NfL distinguished Progressors from Non-Progressors with the highest accuracy (area under the curve 0.92, 90%/87% sensitivity/specificity, 86%/91% positive/negative predictive value, 88% accuracy). Non-Progressor Static tended to have higher T-tau and P-tau levels compared to Non-Progressor Revised Diagnoses. CONCLUSION: This study demonstrated strong diagnostic utility of CSF NfL to distinguish bvFTD from non-progressor variants, at baseline, with high accuracy, in a real-world clinical setting. This has important clinical implications, to improve outcomes for patients and clinicians facing this challenging clinical dilemma, healthcare services, and clinical trials. Further research is required to investigate heterogeneity within the non-progressor group and potential diagnostic algorithms, and prospective studies are underway assessing plasma NfL.


Assuntos
Doença de Alzheimer , Demência Frontotemporal , Humanos , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Filamentos Intermediários , Estudos Prospectivos , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Biomarcadores , Proteínas tau/líquido cefalorraquidiano
15.
Int J Mol Sci ; 23(20)2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36293227

RESUMO

The measurement of serum neurofilament light chain (sNfL) is of growing importance in the field of neurology. In the management of multiple sclerosis, it can serve as a useful marker to assess disease activity and treatment response. This paper compares two available methods, namely the Single Molecule Array (Simoa) and the Ella microfluid platform, to measure longitudinal sNfL levels of 42 highly active multiple sclerosis patients treated with alemtuzumab over a period of 36 months. In order to assess the methods agreement, Bland-Altman plots and Passing-Bablok regression were analyzed. Here, we show that despite the fact that Ella measures around 24% higher values than Simoa, both are equally suitable for longitudinal sNfL monitoring.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/tratamento farmacológico , Filamentos Intermediários , Alemtuzumab , Proteínas de Neurofilamentos , Biomarcadores , Monitorização Fisiológica
16.
Addict Biol ; 27(6): e13232, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36301211

RESUMO

In this translational study, we investigated the plasma tau protein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), which are established biomarkers of neurological injury, as predictive biomarkers of alcohol withdrawal-associated brain toxicity. In the clinical study, patients with severe alcohol use disorder (AUD) on D1 of hospitalization for alcohol cessation (AC) (N = 36) were compared to severe AUD patients with at least 3 months of abstinence (N = 16). Overall, patients were 40 men (76.9%), aged 49.8 years [SD ±9.9]. Tau, NfL, GFAP and UCHL1 levels were measured using SIMOA and analysed with a quasipoisson regression model adjusted for age and sex. The NfL level was higher in the AC group (p = 0.013). In the AC group, the tau (p = 0.021) and UCHL1 (p = 0.021) levels were positively associated with the dose of diazepam per weight, and the tau (p = 0.045), NfL (p = 4.9 × 10-3 ) and UCHL1 (p = 0.036) levels were higher in the presence of signs of Wernicke's encephalopathy (n = 9). In the preclinical study, NfL and GFAP levels were assessed in the alcohol deprivation effect (ADE) procedure (N = 17) and control Wistar rats (N = 15). Furthermore, ADE rats were prospectively assessed: after 24 h (T1) and 3 weeks of AC (T2) (paired-samples Wilcoxon and Mann-Whitney tests). The NfL level was higher in the ADE model than in the control rats at both T1 and T2 (p = 0.033 and p = 1.3 × 10-3 ) and higher at T2 than at T1 (p = 0.040). Plasma tau, NfL and UCHL1 are potential biomarkers of brain suffering during alcohol withdrawal.


Assuntos
Alcoolismo , Síndrome de Abstinência a Substâncias , Animais , Ratos , Proteínas de Neurofilamentos , Proteína Glial Fibrilar Ácida , Ubiquitina Tiolesterase , Projetos Piloto , Estudos de Coortes , Ratos Wistar , Biomarcadores , Encéfalo
20.
Medicine (Baltimore) ; 101(39): e30849, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181119

RESUMO

Neurofilament light chains (NfLs) are promising biomarkers of neuroaxonal damage in stroke patients. We investigated the correlations between NfL levels and infarct volume, initial stroke severity, and functional outcomes at discharge in patients with acute ischemic stroke. We prospectively included 15 patients with first-ever acute ischemic stroke and 8 age- and sex-matched healthy controls without other neurological disorders. Serum NfL levels were measured using the single-molecule array (Simoa) technique twice within 24 hours of admission (NfL1D) and on the seventh hospital day (NfL7D) in patients with stroke and once in healthy controls. We assessed the infarct volume on diffusion-weighted magnetic resonance imaging using the free software ITK-SNAP. Serum NfL1D levels in stroke patients were significantly higher (28.4 pg/mL; interquartile range [IQR], 43.0) than in healthy controls (14.5 pg/mL; IQR, 3.2; P = .005). Temporal pattern analyses demonstrated that NfL7D levels were increased (114.0 pg/mL; IQR, 109.6) compared to NfL1D levels in all stroke patients (P = .001). There was a strong correlation between NfL7D levels and infarct volume (R = 0.67, P = .007). The difference between NfL1D and NfL7D (NfLdiff levels) was strongly correlated with the infarct volume (R = 0.63; P = .013). However, there was no statistically significant correlation between NfL levels and the initial stroke severity or functional outcomes at discharge. NfL levels in the subacute stage of stroke and the NfL difference between admission and 7th day of hospital were correlated with infarct volume in patients with acute ischemic stroke.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Biomarcadores , Humanos , Infarto , Filamentos Intermediários , Proteínas de Neurofilamentos , Acidente Vascular Cerebral/diagnóstico por imagem
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