RESUMEN

Spinocerebellar ataxia type 3 (SCA3) is the most common type of disease related to poly-glutamine (polyQ) repeats. Its hallmark pathology is related to the abnormal accumulation of ataxin 3 with a longer polyQ tract (polyQ-ATXN3). However, there are other mechanisms related to SCA3 progression that require identifying trait and state biomarkers for a more accurate diagnosis and prognosis. Moreover, the identification of potential pharmacodynamic targets and assessment of therapeutic efficacy necessitates valid biomarker profiles. The aim of this review was to identify potential trait and state biomarkers and their potential value in clinical trials. Our results show that, in SCA3, there are different fluid biomarkers involved in neurodegeneration, oxidative stress, metabolism, miRNA and novel genes. However, neurofilament light chain NfL and polyQ-ATXN3 stand out as the most prevalent in body fluids and SCA3 stages. A heterogeneity analysis of NfL revealed that it may be a valuable state biomarker, particularly when measured in plasma. Nonetheless, since it could be a more beneficial approach to tracking SCA3 progression and clinical trial efficacy, it is more convenient to perform a biomarker profile evaluation than to rely on only one.

Asunto(s)

Biomarcadores , Enfermedad de Machado-Joseph , Humanos , Enfermedad de Machado-Joseph/genética , Enfermedad de Machado-Joseph/metabolismo , Enfermedad de Machado-Joseph/patología , Ataxina-3/genética , Ataxina-3/metabolismo , Proteínas de Neurofilamentos/metabolismo , Péptidos/metabolismo , Progresión de la Enfermedad , Estrés Oxidativo

RESUMEN

OBJECTIVE: This study aimed to synthesize the existing evidence on biomarkers related to coronavirus disease 2019 (COVID-19) patients who presented neurological events. METHODS: A systematic review of observational studies (any design) following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Collaboration recommendations was performed (PROSPERO: CRD42021266995). Searches were conducted in PubMed and Scopus (updated April 2023). The methodological quality of nonrandomized studies was assessed using the Newcastle‒Ottawa Scale (NOS). An evidence gap map was built considering the reported biomarkers and NOS results. RESULTS: Nine specific markers of glial activation and neuronal injury were mapped from 35 studies published between 2020 and 2023. A total of 2,237 adult patients were evaluated in the included studies, especially during the acute phase of COVID-19. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) biomarkers were the most frequently assessed (n = 27 studies, 77%, and n = 14 studies, 40%, respectively). Although these biomarkers were found to be correlated with disease severity and worse outcomes in the acute phase in several studies (p < 0.05), they were not necessarily associated with neurological events. Overall, 12 studies (34%) were judged as having low methodological quality, 9 (26%) had moderate quality, and 9 (26%) had high quality. CONCLUSIONS: Different neurological biomarkers in neurosymptomatic COVID-19 patients were identified in observational studies. Although the evidence is still scarce and conflicting for some biomarkers, well-designed longitudinal studies should further explore the pathophysiological role of NfL, GFAP, and tau protein and their potential use for COVID-19 diagnosis and management.

Asunto(s)

COVID-19 , Adulto , Humanos , COVID-19/complicaciones , Prueba de COVID-19 , Lagunas en las Evidencias , Biomarcadores/metabolismo , Neuronas/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo

RESUMEN

Few studies showed that neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tubulin-associated unit (TAU), and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) may be related to neurological manifestations and severity during and after SARS-CoV-2 infection. The objective of this work was to investigate the relationship among nervous system biomarkers (NfL, TAU, GFAP, and UCH-L1), biochemical parameters, and viral loads with heterogeneous outcomes in a cohort of severe COVID-19 patients admitted in Intensive Care Unit (ICU) of a university hospital. For that, 108 subjects were recruited within the first 5 days at ICU. In parallel, 16 mild COVID-19 patients were enrolled. Severe COVID-19 group was divided between "deceased" and "survivor." All subjects were positive for SARS-CoV-2 detection. NfL, total TAU, GFAP, and UCH-L1 quantification in plasma was performed using SIMOA SR-X platform. Of 108 severe patients, 36 (33.33%) presented neurological manifestation and 41 (37.96%) died. All four biomarkers - GFAP, NfL, TAU, and UCH-L1 - were significantly higher among deceased patients in comparison to survivors (p < 0.05). Analyzing biochemical biomarkers, higher Peak Serum Ferritin, D-Dimer Peak, Gamma-glutamyltransferase, and C-Reactive Protein levels were related to death (p < 0.0001). In multivariate analysis, GFAP, NfL, TAU, UCH-L1, and Peak Serum Ferritin levels were correlated to death. Regarding SARS-CoV-2 viral load, no statistical difference was observed for any group. Thus, Ferritin, NFL, GFAP, TAU, and UCH-L1 are early biomarkers of severity and lethality of SARS-COV-2 infection and may be important tools for therapeutic decision-making in the acute phase of disease.

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BACKGROUND: Neurofilament Light (NfL) chain levels in both cerebrospinal fluid (CSF) and serum have been correlated with the reduction of axonal damage in multiple sclerosis (MS) patients treated with Natalizumab (NTZ). However, little is known about the function of plasmacytoid cells in NTZ-treated MS patients. OBJECTIVE: To evaluate CSF NfL, serum levels of soluble-HLA-G (sHLA-G), and eventual tolerogenic behavior of plasmacytoid dendritic cells (pDCs) in MS patients during NTZ treatment. METHODS: CSF NfL and serum sHLA-G levels were measured using an ELISA assay, while pDCs (BDCA-2+) were accessed through flow cytometry analyses. RESULTS: CSF levels of NfL were significantly reduced during NTZ treatment, while the serum levels of sHLA-G were increased. Moreover, NTZ treatment enhanced tolerogenic (HLA-G+, CD274+, and HLA-DR+) molecules and migratory (CCR7+) functions of pDCs in the peripheral blood. CONCLUSION: These findings suggest that NTZ stimulates the production of molecules with immunoregulatory function such as HLA-G and CD274 programmed death-ligand 1 (PD-L1) which may contribute to the reduction of axonal damage represented by the decrease of NfL levels in patients with MS.

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INTRODUCTION: This study characterized the relationship between plasma NfL and cognition in a community-based sample of older Mexican Americans. METHODS: 544 participants completed a battery of neuropsychological tests and were diagnosed using clinical criteria. NfL was assayed using Simoa. NfL levels across groups and tests were analyzed. RESULTS: Difference in NfL was found between normal and impaired groups and was related to global cognition, processing speed, executive functions and a list of learning tasks with a significant negative effect for all diagnostic groups. NfL had a negative impact on processing speed, attention, executive functions and delayed and recognition memory for both normal and MCI groups. CONCLUSION: The research supports plasma NfL as a marker of cognitive impairment related to neurodegenerative processes in Mexican Americans and may be a marker of early changes in cognition in those with normal cognition and at risk for developing MCI.

Asunto(s)

Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Biomarcadores/sangre , Cognición/fisiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Americanos Mexicanos/estadística & datos numéricos , Proteínas de Neurofilamentos/metabolismo , Factores de Edad , Anciano , Enfermedad de Alzheimer/sangre , Disfunción Cognitiva/sangre , Función Ejecutiva , Femenino , Voluntarios Sanos , Humanos , Vida Independiente , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos

RESUMEN

BACKGROUND: Primary central nervous system (CNS) tumors and brain metastases (BMs) are major causes of morbidity and mortality, accompanied by low survival rates. Efforts to early discovery of CNS malignancies are critical. However, to date, there are no biomarkers approved for detection of cancer activity in the brain. Blood levels of neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp), show promise as biomarkers for brain injury in previous studies. Therefore, we performed a cross-sectional study to investigate correlations of those biomarkers with CNS activity of gliomas and BMs. METHODS: Serum samples of 36 participants of a single centered institution were tested for NfL, GFAp and tau with Simoa immunoassay, and correlated with clinical and radiological data. RESULTS: NfL and GFAp levels were significantly associated with the state of intracranial disease (analysis of variance (ANOVA), PsNfL = 0.03; ANOVA, PGFAp = 0.03). Although statistically significant (P = 0.04), differences in concentrations were not clinically meaningful for tau levels. Serum NfL (sNfL) and GFAp concentrations were higher in the group of patients with CNS tumors with disease in progression versus CNS with stable disease (P = 0.03 and P = 0.01, respectively). In addition, sNfL were higher in patients with metastatic solid tumors with known BMs than in those with metastatic tumors with no BM (P = 0.0004). CONCLUSION: sNfL and GFAp both apparently vary closely with presence and activity of gliomas and BMs. Further studies in larger populations are needed to expand these findings.