Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 73
Filtrar
1.
J Clin Neurosci ; 76: 41-45, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32327377

RESUMEN

This paper aims to investigate the possible roles of a set of neurotrophic factors (brain-derived neurotrophic factor-BDNF, nerve growth factor-NGF) and neuropeptides (neuropeptide Y-NPY, and galanin) in children with active epileptogenesis. The cerebrospinal fluid (CSF) levels of BDNF, NPY, NGF and galanin were measured with enzyme-linked immunosorbent assays in epileptic children (n = 73) and controls (n = 64). There were no significant alterations in the CSF levels of BDNF, NPY and NGF in epileptic children with active clinical seizures compared with the levels of controls. However profoundly depressed galanin levels were found in infants with epileptic encephalopathy (mean ± SD:0.63 ± 0.19 pg/ml) and significantly increased galanin levels were measured in children with drug resistant epilepsy during the period of status epilepticus (mean ± SD: 6.92 ± 1.19, pg/ml pg/ml) compared with the levels of controls. Depressed levels of galanin might reflect a defective anti-epileptogenic effect of galanin in infants with epileptic encephalopathy. On the contrary, increased CSF levels of galanin might be a result of anti-epileptogenic effects of this peptide in epileptic children with status epilepticus.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Epilepsia/líquido cefalorraquídeo , Galanina/líquido cefalorraquídeo , Factor de Crecimiento Nervioso/líquido cefalorraquídeo , Neuropéptido Y/líquido cefalorraquídeo , Animales , Niño , Femenino , Humanos , Lactante , Masculino , Estado Epiléptico/líquido cefalorraquídeo
2.
Int J Mol Sci ; 21(3)2020 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-32041109

RESUMEN

Amyotrophic lateral sclerosis (ALS) remains a fatal disease with limited therapeutic options. Signaling via neurotrophins (NTs), neuroinflammation, and certain micro-RNAs are believed to play essential role in ALS pathogenesis. Lineage-negative stem/progenitor cells (Lin-) were obtained from bone marrow of 18 ALS patients and administered intrathecally. Clinical assessment was performed using ALS Functional Rating Scale (FRSr) and Norris scale. Protein concentrations were measured in plasma and cerebrospinal fluid (CSF) by multiplex fluorescent bead-based immunoassay. Gene expression in nucleated blood cells was assessed using gene microarray technique. Finally, miRNA expression was analyzed using qPCR in CSF and plasma samples. We observed a significant decrease of C-reactive protein (CRP) concentration in plasma on the seventh day from the application of cells. Gene array results revealed decreased expression of gene sets responsible for neutrophil activation. Further analysis revealed moderate negative correlation between CRP level in CSF and clinical outcome. Brain-derived neurotrophic factor (BDNF) concentrations in both plasma and CSF significantly correlated with the favorable clinical outcome. On a micro-RNA level, we observed significant increase of miR-16-5p expression one week after transplantation in both body fluids and significant increase of miR-206 expression in plasma. Administration of Lin- cells may decrease inflammatory response and prevent neurodegeneration. However, these issues require further investigations.


Asunto(s)
Esclerosis Amiotrófica Lateral/terapia , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteína C-Reactiva/metabolismo , MicroARNs/sangre , MicroARNs/genética , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/inmunología , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Proteína C-Reactiva/líquido cefalorraquídeo , Linaje de la Célula , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Inmunidad Humoral , Inyecciones Espinales , MicroARNs/líquido cefalorraquídeo , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Trasplante de Células Madre
3.
Pharmacol Rep ; 71(4): 669-675, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31195344

RESUMEN

BACKGROUND: Neurotrophins, especially brain-derived neurotrophic factor (BDNF) have gained significant therapeutic interest particularly in neurologic and psychiatric disorders and they have been found in human breast milk of mothers who suffered from adverse outcomes in pregnancy. This study tested the hypothesis that oral administration of BDNF/GDNF (glial cell line-derived neurotrophic factor) can exert a biological effect in a rat model of severe neuropathology induced by olfactory bulbectomy (OBX), which exhibits dysregulation of BDNF signaling and impaired blood-brain barrier. METHODS: Adult male albino Sprague-Dawley rats underwent the OBX surgery and separate groups of OBX and sham-operated controls received one oral dose of vehicle, BDNF (0.005 mg/kg), GDNF (0.03 mg/kg) or their combination. One week after neurotrophin dosing the rats were sacrificed and BDNF level was assessed by ELISA in the blood serum and cerebrospinal fluid. RESULTS: A significant decrease of serum BDNF level was found in the OBX model. This alteration was normalized by all types of treatment BDNF, GDNF, or their combination. No influence of sham surgery or treatment was observed in the control rats. BDNF levels in cerebrospinal fluid were below detection limit. CONCLUSION: This study indicates that oral administration of neurotrophins is able to exert a biological effect in the OBX model. There is a number of potential mechanisms, which remain to be elucidated.


Asunto(s)
Barrera Hematoencefálica/metabolismo , Encefalopatías/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Factores de Crecimiento Nervioso/sangre , Administración Oral , Animales , Transporte Biológico , Barrera Hematoencefálica/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/administración & dosificación , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Modelos Animales de Enfermedad , Masculino , Factores de Crecimiento Nervioso/administración & dosificación , Factores de Crecimiento Nervioso/líquido cefalorraquídeo , Bulbo Olfatorio/cirugía , Prueba de Estudio Conceptual , Ratas Sprague-Dawley , Proteínas Recombinantes
4.
Cell Tissue Res ; 377(1): 73-79, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31076872

RESUMEN

Most growth factors are synthesized as precursors and biologically active forms are generated by proteolytic cleavage of the pro-domain. However, the biological functions of pro-domains are ill-defined. New roles were recently reported for the pro-domain of brain-derived neurotrophic factor (BDNF), a well-known growth factor in the brain. Interestingly, the pro-domain of BDNF (BDNF pro-peptide) is localized at presynaptic termini, where it facilitates long-term depression (LTD) in hippocampal slices, implicating it as a novel synaptic modulator. BDNF binds its pro-peptide with high affinity in a pH-dependent manner and when bound to BDNF, the BDNF pro-peptide cannot facilitate hippocampal LTD, representing a new mechanism of regulation. The BDNF pro-peptide is present in human cerebrospinal fluid (CSF) and levels were significantly lower in patients with major depressive disorder (MDD) than in controls. Notably, male MDD patients exhibit significantly lower levels of CSF pro-peptide than females. These findings demonstrate that the BDNF pro-peptide is a biologically important synaptic modulator and is associated with MDD, particularly in males.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Trastorno Depresivo Mayor/metabolismo , Hipocampo/metabolismo , Depresión Sináptica a Largo Plazo/fisiología , Neurotransmisores/metabolismo , Terminales Presinápticos/metabolismo , Animales , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Femenino , Humanos , Masculino , Ratones , Precursores de Proteínas/líquido cefalorraquídeo , Precursores de Proteínas/metabolismo , Ratas , Transmisión Sináptica
5.
J Psychiatr Res ; 113: 190-198, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30986693

RESUMEN

The role of brain-derived neurotrophic factor (BDNF) and its related molecules has been extensively studied in the context of psychiatric disorders. In the present study, we focused on the newly identified BDNF pro-peptide, which is generated together with mature BDNF by proteolytic processing of their precursor, proBDNF. Here, we report, for the first time, that BDNF pro-peptide is present in human cerebrospinal fluid (CSF) and quantifiable by western blotting. We measured CSF BDNF pro-peptide levels in 27 patients with schizophrenia, 18 patients with major depressive disorder (MDD), and 27 healthy controls matched for age, sex, and ethnicity (Japanese). The ratio of the BDNF pro-peptide level to the total protein level in MDD patients was significantly lower than that in controls (Kruskal-Wallis with Dunn's multiple comparisons test; p = 0.046). When men and women were examined separately, males with MDD had a significantly lower BDNF pro-peptide/protein ratio than male controls (p = 0.047); this difference was not found in female subjects. The ratio tended to be lower in male schizophrenia patients (p = 0.10). Although we tried to measure the levels of mature BDNF in CSF, they were below the limit of detection of the ELISA and multiple analyte profiling technology. Taken together, the results suggest that reduced CSF BDNF pro-peptide levels are associated with MDD, particularly in males. Further studies involving a larger sample size are warranted.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Trastorno Depresivo Mayor/líquido cefalorraquídeo , Esquizofrenia/líquido cefalorraquídeo , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad
6.
Mol Neurobiol ; 56(6): 4364-4380, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30317434

RESUMEN

Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) displays a promising antidepressant effects in patients with treatment-refractory depression; however, a clear consensus on underlying mechanisms is still enigmatic. Herein, we investigated the effects of MFB-DBS on anhedonic-like behavior using the Froot Loops® consumption in a chronic unpredictable mild stress (CUS) model of depression, biochemical estimation of peripheral and central inflammatory cytokines, stress hormone, and brain-derived neurotrophic factor (BDNF). Seven days of MFB-DBS significantly reversed the 42-day CUS-generated anhedonic-like phenotype (p < 0.02) indicated by an increase in Froot Loops® consumption. Gross locomotor activity and body weight remained unaffected across the different groups. A dramatic augmentation of adrenocorticotropic hormone levels was seen in the plasma and cerebrospinal fluid (CSF) samples of CUS rats, which significantly reduced following MFB-DBS treatment. However, C-reactive protein levels were found to be unaffected. Interestingly, decreased levels of BDNF in the CUS animals were augmented in the plasma, CSF, and hippocampus following MFB-DBS, but remained unaltered in the nucleus accumbens (NAc). While multiplex assay revealed no change in the neuronal levels of inflammatory cytokines including IL-1α, IL-4, IL-10, IL-12, IL-13, and IL-17 in the neuroanatomical framework of the hippocampus and NAc, increased levels of IL-1ß, IL-2, IL-5, IL-6, IL-7, IL-18, TNF-α, and INF-γ were seen in these brain structures after CUS and were differentially modulated in the presence of MFB stimulation. Here, we show that there is dysregulation of BDNF and neuroimmune mediators in a stress-driven chronic depression model, and that chronic MFB-DBS has the potential to undo these aberrations.


Asunto(s)
Anhedonia , Conducta Animal , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Citocinas/metabolismo , Estimulación Encefálica Profunda , Depresión/complicaciones , Mediadores de Inflamación/metabolismo , Haz Prosencefálico Medial/patología , Hormona Adrenocorticotrópica/sangre , Hormona Adrenocorticotrópica/líquido cefalorraquídeo , Animales , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Proteína C-Reactiva/líquido cefalorraquídeo , Proteína C-Reactiva/metabolismo , Depresión/sangre , Depresión/líquido cefalorraquídeo , Depresión/fisiopatología , Modelos Animales de Enfermedad , Conducta Alimentaria , Hipocampo/metabolismo , Masculino , Actividad Motora , Núcleo Accumbens/metabolismo , Ratas Wistar , Estrés Psicológico/sangre , Estrés Psicológico/líquido cefalorraquídeo , Estrés Psicológico/complicaciones , Estrés Psicológico/fisiopatología
7.
Ann Neurol ; 84(3): 424-435, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30014553

RESUMEN

OBJECTIVE: Previous studies suggest that the brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism may influence symptom onset in Alzheimer's disease (AD). Our recent cross-sectional findings suggest that Met66 may influence clinical expression in dominantly inherited AD (DIAD) through its effects on tau. However, it remains unclear whether carriage of Met66 in DIAD results in faster increases in cerebrospinal fluid (CSF) tau and ptau181 , and whether these increases are associated with accelerated brain volume loss and memory decline. METHODS: A total of 211 subjects (101 mutation noncarriers, 110 mutation carriers), who were cognitively normal, as defined by a Clinical Dementia Rating global score of 0, completed assessments of cognitive function, neuroimaging, and CSF sampling over 3.5 years as part of the Dominantly Inherited Alzheimer's Network. RESULTS: In mutation carriers, Met66 carriers showed faster memory decline (4×), hippocampal volume loss (16×), and CSF tau and ptau181 increases (6×) than Val66 homozygotes. BDNF did not influence rates of cortical ß-amyloid accumulation or change in CSF Aß42 levels in mutation carriers. In mutation noncarriers, BDNF genotype had no effect on change in cognition, brain volume, cortical ß-amyloid accumulation, or change in any CSF measures of tau, ptau181 , and CSF Aß42 . INTERPRETATION: As in sporadic AD, the deleterious effects of ß-amyloid on cognitive function, brain volume loss, and CSF tau in DIAD mutation carriers are less in Val66 homozygotes. The BDNF Val66Met polymorphism should be considered as a potential moderator of clinical trial outcomes in current treatment and prevention trials in DIAD and sporadic AD. Ann Neurol 2018;84:424-435.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Encéfalo/metabolismo , Proteínas tau/líquido cefalorraquídeo , Adulto , Anciano , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Cognición/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/líquido cefalorraquídeo , Fragmentos de Péptidos/metabolismo , Proteínas tau/metabolismo
8.
J Mol Neurosci ; 65(3): 289-300, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29956088

RESUMEN

Accumulating evidence suggest that aberrations of neurotrophic factors are involved in the etiology and pathogenesis of Alzheimer's disease (AD), but clinical data were inconsistent. Therefore, a meta-analysis on neurotrophic factor levels in AD is necessary. We performed a systematic review of blood, CSF, and post-mortem brain neurotrophic factor levels in patients with AD compared with controls and quantitatively summarized the clinical data in blood and CSF with a meta-analytical technique. A systematic search of PubMed and Web of Science identified 98 articles in this study (with samples more than 9000). Random effects meta-analysis demonstrated that peripheral blood BDNF levels were significantly decreased in AD patients compared with controls. However, blood NGF, IGF, and VEGF did not show significant differences between cases and controls. In CSF, random effects meta-analysis showed significantly deceased BDNF and increased NGF levels in patients with AD, whereas IGF and VEGF did not show significant differences between the AD group and control group. In addition, 23 post-mortem studies were included in the systematic review. Although data from post-mortem brains were not always consistent across studies, most studies suggested decreased BDNF and increased (pro)NGF levels in hippocampus and neocortex of patients with AD. These results provide strong clinical evidence that AD is accompanied by an aberrant neurotrophin profile, and future investigations into neurotrophins as biomarkers (especially CSF BDNF and NGF) and therapeutic targets for AD may be warranted.


Asunto(s)
Enfermedad de Alzheimer/sangre , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Encéfalo/metabolismo , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/patología , Autopsia , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/metabolismo , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Humanos
9.
Exp Gerontol ; 110: 54-60, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29775745

RESUMEN

Midbrain dopamine neuronal loss and neuroinflammation are two phenomena that are associated with brain senescence. Neurotrophic factor changes and oxidative stress could subserve these phenomena. Aging-related brain changes can be well monitored through the cerebrospinal fluid (CSF). The objective was to analyze neurotrophic and oxidative parameters that could be related to midbrain dopamine neuronal loss or brain inflammation in the CSF of elderly subjects: 1) levels of the dopaminotrophic factors BDNF, GDNF, persephin, and neurturin, 2) levels of the proinflammatory factors TGFß1 and TGFß2; 3) activity of main antioxidant enzymes (catalases, glutathione-peroxidase, glutathione-reductase, glutathione-S-transferases, peroxirredoxins, and superoxide-dismutases), 4) ferritin content, antioxidant protein which reduces reactive free iron, and 5) antioxidant potential of the cerebrospinal fluid. ELISA and PAO tests were used. Subjects were also evaluated clinically, and the group of old subjects with mild cognitive impairment was studied separately. The findings indicate that normal elderly CSF is devoid of changes in either dopaminotrophic or proinflammatory factors. The antioxidant efficacy is slightly reduced with normal aging, through a reduction of glutathione-S-transferase activity in people older than 74 years (p < 0.05). However old people with mild cognitive impairment show reduced BDNF levels, and stronger signs of oxidative stress such as low antioxidant potential and glutathione-S-transferase activity (p < 0.05). To sum up, the present study demonstrates that, in CSF of normal senescence, dopaminotrophic factors and proinflammatory TGF-family ligands are not affected, and antioxidant efficacy is slightly reduced. CSF of elderly subjects with mild cognitive impairment shows more oxidative and trophic changes that are characterized by reduction of BDNF content, glutathione-S-transferase activity, and antioxidant potential.


Asunto(s)
Envejecimiento/metabolismo , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Dopamina/metabolismo , Glutatión Transferasa/líquido cefalorraquídeo , Mesencéfalo/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antioxidantes/metabolismo , Disfunción Cognitiva/líquido cefalorraquídeo , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Crecimiento Nervioso/líquido cefalorraquídeo , Estrés Oxidativo , Adulto Joven
10.
J Neurotrauma ; 35(17): 2044-2055, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-29732941

RESUMEN

Until now, it is impossible to identify a fatal traumatic brain injury (TBI) before post-mortem radiological investigations or an autopsy take place. It would be preferable to have an additional diagnostic tool such as post-mortem biochemistry to get greater insight into the pathological pathways and survival times after sustaining TBI. Cerebrospinal fluid (CSF) and serum samples of 84 autopsy cases were collected from forensic autopsies with post-mortem intervals (PMI) of up to 148 h. The cases were categorized into a fatal TBI case group (n = 42) and non-TBI controls (n = 42). The values of glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), and neutrophil gelatinase-associated lipocalin (NGAL) were analyzed by means of quantitative chemiluminescent multiplex immunoassays. The main results indicate that the usage of liquid samples with good macroscopic quality is more relevant for meaningful biomarker analyses than the length of the PMI. All three proteins were shown to differentiate TBI fatalities from the controls in CSF. In serum, only GFAP could be shown to be able to identify TBI cases. This study is the first approach to measure the three proteins together in CSF and serum in autopsy cases. Determined threshold values may differentiate between fatal TBI and control cases. The presented results emphasize the possible use of post-mortem biochemistry as a supplemental tool in everyday forensic routine.


Asunto(s)
Líquidos Corporales/química , Química Encefálica , Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/líquido cefalorraquídeo , Proteínas del Tejido Nervioso/sangre , Proteínas del Tejido Nervioso/líquido cefalorraquídeo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Autopsia , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Lesiones Traumáticas del Encéfalo/diagnóstico , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Estudios de Casos y Controles , Causas de Muerte , Femenino , Patologia Forense , Proteína Ácida Fibrilar de la Glía/sangre , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Humanos , Lipocalina 2/sangre , Lipocalina 2/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Cambios Post Mortem , Análisis de Supervivencia , Adulto Joven
11.
Psychiatry Res ; 265: 25-38, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29680514

RESUMEN

Over the last decade, finding a reliable biomarker for the early detection of schizophrenia (Scz) has been a topic of interest. The main goal of the current review is to provide a comprehensive view of the brain, blood, cerebrospinal fluid (CSF), and serum biomarkers of Scz disease. Imaging studies have demonstrated that the volumes of the corpus callosum, thalamus, hippocampal formation, subiculum, parahippocampal gyrus, superior temporal gyrus, prefrontal and orbitofrontal cortices, and amygdala-hippocampal complex were reduced in patients diagnosed with Scz. It has been revealed that the levels of interleukin 1ß (IL-1ß), IL-6, IL-8, and TNF-α were increased in patients with Scz. Decreased mRNA levels of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), neurotrophin-3 (NT-3), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) genes have also been reported in Scz patients. Genes with known strong relationships with this disease include BDNF, catechol-O-methyltransferase (COMT), regulator of G-protein signaling 4 (RGS4), dystrobrevin-binding protein 1 (DTNBP1), neuregulin 1 (NRG1), Reelin (RELN), Selenium-binding protein 1 (SELENBP1), glutamic acid decarboxylase 67 (GAD 67), and disrupted in schizophrenia 1 (DISC1). The levels of dopamine, tyrosine hydroxylase (TH), serotonin or 5-hydroxytryptamine (5-HT) receptor 1A and B (5-HTR1A and 5-HTR1B), and 5-HT1B were significantly increased in Scz patients, while the levels of gamma-aminobutyric acid (GABA), 5-HT transporter (5-HTT), and 5-HT receptor 2A (5-HTR2A) were decreased. The increased levels of SELENBP1 and Glycogen synthase kinase 3 subunit α (GSK3α) genes in contrast with reduced levels of B-cell translocation gene 1 (BTG1), human leukocyte antigen DRB1 (HLA-DRB1), heterogeneous nuclear ribonucleoprotein A3 (HNRPA3), and serine/arginine-rich splicing factor 1 (SFRS1) genes have also been reported. This review covers various dysregulation of neurotransmitters and also highlights the strengths and weaknesses of studies attempting to identify candidate biomarkers.


Asunto(s)
Encéfalo/metabolismo , Esquizofrenia/sangre , Esquizofrenia/líquido cefalorraquídeo , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/metabolismo , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Catecol O-Metiltransferasa/sangre , Catecol O-Metiltransferasa/líquido cefalorraquídeo , Catecol O-Metiltransferasa/metabolismo , Moléculas de Adhesión Celular Neuronal/sangre , Moléculas de Adhesión Celular Neuronal/líquido cefalorraquídeo , Moléculas de Adhesión Celular Neuronal/metabolismo , Disbindina/sangre , Disbindina/líquido cefalorraquídeo , Disbindina/metabolismo , Proteínas de la Matriz Extracelular/sangre , Proteínas de la Matriz Extracelular/líquido cefalorraquídeo , Proteínas de la Matriz Extracelular/metabolismo , Humanos , Factores de Crecimiento Nervioso/sangre , Factores de Crecimiento Nervioso/líquido cefalorraquídeo , Factores de Crecimiento Nervioso/metabolismo , Proteínas del Tejido Nervioso/sangre , Proteínas del Tejido Nervioso/líquido cefalorraquídeo , Proteínas del Tejido Nervioso/metabolismo , Neurotrofina 3 , Corteza Prefrontal/metabolismo , Esquizofrenia/diagnóstico por imagen , Serina Endopeptidasas/sangre , Serina Endopeptidasas/líquido cefalorraquídeo , Serina Endopeptidasas/metabolismo , Factor A de Crecimiento Endotelial Vascular
12.
PLoS One ; 12(11): e0187013, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29190741

RESUMEN

BACKGROUND: An imbalance in the excitatory/inhibitory systems in the pain networks may explain the persistent chronic pain after hallux valgus surgery. Thus, to contra-regulate this dysfunction, the use of transcranial direct current stimulation (tDCS) becomes attractive. OBJECTIVE: We tested the hypothesis that two preoperative active(a)-tDCS sessions compared with sham(s)-tDCS could improve the postoperative pain [as indexed by Visual Analogue Scale (VAS) at rest and during walking (primary outcomes)]. To assess their effect on the change in the Numerical Pain Scale (NPS0-10) during Conditioned Pain Modulation (CPM-task), disability related to pain (DRP) and analgesic consumption (secondary outcomes). Also, we assessed if the brain derived neurotrophic factor (BDNF) in the cerebral spinal fluid (CSF) after tDCS could predict the intervention's effect on the DRP. METHODS: It is a prospective, double blind, sham-controlled, randomized single center, 40 women (18-70 years-old) who had undergone hallux valgus surgery were randomized to receive two sessions (20 minutes each) of anodal a-tDCS or s-tDCS on the primary motor cortex at night and in the morning before the surgery. To assess the DRP was used the Brazilian Profile of Chronic Pain: Screen (B-PCP:S). RESULTS: A-tDCS group showed lower scores on VAS at rest and during walking (P<0.001). At rest, the difference between groups was 2.13cm (95%CI = 1.59 to 2.68) while during walking was 1.67cm (95%CI = 1.05 to 2.28). A-tDCS, when compared to s-tDCS reduced analgesic doses in 73.25% (P<0.001), produced a greater reduction in B-PCP:S (mean difference of 9.41 points, 95%CI = 0.63 to 18.21) and higher function of descending pain modulatory system (DPMS) during CPM-task. CONCLUSION: A-tDCS improves postoperative pain, the DRP and the function of DPMS. Also, the CSF BDNF after a-tDCS predicted the improvement in the DRP. In overall, these findings suggest that a-tDCS effects may be mediated by top-down regulatory mechanisms associated with the inhibitory cortical control. TRIAL REGISTRATION: ClinicalTrials.gov NCT02360462.


Asunto(s)
Hallux Valgus/cirugía , Plasticidad Neuronal , Dolor Postoperatorio/terapia , Cuidados Preoperatorios , Estimulación Transcraneal de Corriente Directa , Adulto , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Dolor Crónico , Método Doble Ciego , Femenino , Humanos , Persona de Mediana Edad , Dolor Postoperatorio/metabolismo , Estudios Prospectivos
13.
Transl Psychiatry ; 7(1): e995, 2017 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-28072416

RESUMEN

Brain autopsy and biomarker studies indicate that the pathology of Alzheimer's disease (AD) is initiated at least 10-20 years before clinical symptoms. This provides a window of opportunity to initiate preventive treatment. However, this emphasizes the necessity for biomarkers that identify individuals at risk for developing AD later in life. In this cross-sectional study, originating from three epidemiologic studies in Sweden (n=1428), the objective was to examine whether amyloid pathology, as determined by low cerebrospinal fluid (CSF) concentration of the 42 amino acid form of ß-amyloid (Aß42), is associated with biomarker evidence of other pathological changes in cognitively healthy elderly. A total of 129 patients were included and CSF levels of Aß42, total tau, tau phosphorylated at threonine 181 (p-tau), neurogranin, VILIP-1, VEGF, FABP3, Aß40, neurofilament light, MBP, orexin A, BDNF and YKL-40 were measured. Among these healthy elderly, 35.6% (N=46) had CSF Aß42 levels below 530 pg ml-1. These individuals displayed significantly higher CSF concentrations of t-tau (P<0.001), p-tau (181) (P<0.001), neurogranin (P=0.009) and FABP3 (P=0.044) compared with amyloid-negative individuals. Our study indicates that there is a subpopulation among healthy older individuals who have amyloid pathology along with signs of ongoing neuronal and synaptic degeneration, as well as tangle pathology. Previous studies have demonstrated that increase in CSF tau and p-tau is a specific sign of AD progression that occurs downstream of the deposition of Aß. On the basis of this, our data suggest that these subjects are at risk for developing AD. We also confirm the association between APOE ɛ4 and amyloid pathology in healthy older individuals.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/líquido cefalorraquídeo , Apolipoproteína E4/genética , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Proteína 1 Similar a Quitinasa-3/líquido cefalorraquídeo , Estudios Transversales , Proteína 3 de Unión a Ácidos Grasos/líquido cefalorraquídeo , Femenino , Voluntarios Sanos , Humanos , Masculino , Proteína Básica de Mielina/líquido cefalorraquídeo , Neurocalcina/líquido cefalorraquídeo , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Neurogranina/líquido cefalorraquídeo , Orexinas/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo , Fosfoproteínas/líquido cefalorraquídeo , Suecia , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo
14.
Int J Neurosci ; 127(1): 44-50, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26732732

RESUMEN

No biomarker has been established as a prognostic indicator of acute encephalopathy associated with various etiological factors. In this study, we examined useful prognostic biomarkers in patients with acute encephalopathy associated with respiratory syncytial virus (RSV) infection. The subjects were 11 children with RSV-associated encephalopathy admitted to our hospital. We measured the levels of interleukin (IL)-6, brain-derived neurotrophic factor (BDNF) and nitrogen oxide (NO)x in cerebrospinal fluid collected on the day of admission. Using the pediatric cerebral performance categories (PCPC) score as a prognostic indicator, we evaluated the association between the biomarkers and neurologic prognosis. Concerning neurologic prognosis, sequelae were noted in more than 50% of the subjects. There was no association between prognosis and age/sex. Increases in the levels of all biomarkers were observed in all subjects. IL-6 and BDNF levels were correlated with PCPC score, but not with NOx. Of the biomarkers investigated, the IL-6 and BDNF levels in cerebrospinal fluid were shown to be correlated with neurologic prognosis. Because many patients with this disease had severe sequelae, assessment should be conducted by early evaluation of the biomarkers examined in this study with respect to the clinical course.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Encefalitis Viral/líquido cefalorraquídeo , Encefalitis Viral/fisiopatología , Interleucina-6/líquido cefalorraquídeo , Óxidos de Nitrógeno/líquido cefalorraquídeo , Infecciones por Virus Sincitial Respiratorio/líquido cefalorraquídeo , Índice de Severidad de la Enfermedad , Adolescente , Biomarcadores/líquido cefalorraquídeo , Niño , Preescolar , Femenino , Humanos , Masculino , Pronóstico
15.
Neurosci Lett ; 637: 108-113, 2017 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-27888042

RESUMEN

Inflammatory and neurotrophic factors are involved in postherpetic neuralgia (PHN), but the association of these factors in the cerebrospinal fluid (CSF) with the level of pain is poorly known. The present study aimed to examine the changes in neurotrophic and inflammatory factors in the CSF of patients with PHN and to study the correlation between these factors and the degree of pain. Fifty patients with PHN and 28 patients with hemifacial spasm (as controls) were recruited between May 2015 and March 2016. CSF levels of inflammatory and neurotrophic factors were measured by ELISA. Compared with controls, patients with PHN had lower CSF levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin (NT)-3, NT-5, and P substance (all P<0.05), and higher CSF levels of interleukin (IL)-1ß (P=0.050). Among patients with PHN, CSF BDNF levels were positively correlated to IL-8 (rs=0.229, P=0.04); glial cell line-derived neurotrophic factor (GDNF) levels to IL-8 (rs=0.326, P=0.004) levels; NGF levels to tumor necrosis factor (TNF)-α levels (rs=0.229, P=0.044); NT-3 levels to IL-1ß (rs=0.228, P=0.045); and NT-5 levels to IL-8 (rs=0.388, P<0.001), and TNF-α (rs=0.445, P<0.001) levels. Inflammatory and neurotrophic factors were not correlated with the visual analog scale score and von Frey. Multivariable linear regression showed PHN was associated with NGF (P=0.038) and BDNF (P=0.029), independently from age and major medical history. In conclusion, patients with PHN showed low levels of BDNF, NGF, NT-3, and NT-5. Among patients with PHN, CSF levels of neurotrophic factors positively correlated with inflammatory factors.


Asunto(s)
Inflamación/líquido cefalorraquídeo , Neuralgia Posherpética/líquido cefalorraquídeo , Anciano , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Femenino , Humanos , Interleucina-1beta/líquido cefalorraquídeo , Interleucina-8/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Factor de Crecimiento Nervioso/líquido cefalorraquídeo , Neurotrofina 3/líquido cefalorraquídeo
16.
J Neurovirol ; 23(3): 369-375, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-27995575

RESUMEN

In the USA, increased cerebrospinal fluid (CSF) inflammatory cytokines have been observed in antiretroviral therapy (ART)-naive, HIV-seropositive individuals with HIV-associated neurocognitive disorder (HAND). We characterized the relationship between HAND and CSF biomarker expression in ART-naive, HIV-seropositive individuals in Rakai, Uganda. We analyzed CSF of 78 HIV-seropositive, ART-naive Ugandan adults for 17 cytokines and 20 neurodegenerative biomarkers via Luminex multiplex assay. These adults underwent neurocognitive assessment to determine their degree of HAND. We compared biomarker concentrations between high and low CD4 groups and across HAND classifications, adjusting for multiple comparisons. Individuals with CD4 <200 cells/µL (N = 38) had elevated levels of CSF Interleukin (IL)-2, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF-α, matrix metalloproteinase (MMP)-1, MMP-7, and S100 calcium-binding protein B (S100B) and lower levels of amyloid ß42. Individuals with CD4 351-500 cells/µL (N = 40) had significantly higher CSF levels of interleukin (IL)-1ß, amyloid ß42, and soluble receptor for advanced glycation end products (sRAGE). Increasing levels of S100B, platelet-derived growth factor-AA (PDGF-AA), brain-derived neurotrophic factor (BDNF), and sRAGE were associated with decreased odds of mild neurocognitive disorder (n = 22) or HIV-associated dementia (n = 15) compared with normal function (n = 30) or asymptomatic neurocognitive impairment (n = 11). Increased levels of interferon (IFN)-γ were associated with increased odds of mild neurocognitive impairment or HIV-associated dementia relative to normal or asymptomatic neurocognitive impairment. Proinflammatory CSF cytokines, chemokines, and neurodegenerative biomarkers were present in increasing concentrations with advanced immunosuppression and may play a role in the development of HAND. The presence of select CNS biomarkers may also play a protective role in the development of HAND.


Asunto(s)
Complejo SIDA Demencia/líquido cefalorraquídeo , Complejo SIDA Demencia/diagnóstico , Linfocitos T CD4-Positivos/inmunología , Complejo SIDA Demencia/inmunología , Complejo SIDA Demencia/fisiopatología , Adulto , Péptidos beta-Amiloides/líquido cefalorraquídeo , Péptidos beta-Amiloides/inmunología , Biomarcadores/líquido cefalorraquídeo , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Factor Neurotrófico Derivado del Encéfalo/inmunología , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/patología , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/líquido cefalorraquídeo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Humanos , Interleucina-12/líquido cefalorraquídeo , Interleucina-12/inmunología , Interleucina-2/líquido cefalorraquídeo , Interleucina-2/inmunología , Masculino , Metaloproteinasa 1 de la Matriz/líquido cefalorraquídeo , Metaloproteinasa 1 de la Matriz/inmunología , Metaloproteinasa 7 de la Matriz/líquido cefalorraquídeo , Metaloproteinasa 7 de la Matriz/inmunología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Fragmentos de Péptidos/líquido cefalorraquídeo , Fragmentos de Péptidos/inmunología , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Factor de Crecimiento Derivado de Plaquetas/inmunología , Estudios Prospectivos , Receptor para Productos Finales de Glicación Avanzada/sangre , Receptor para Productos Finales de Glicación Avanzada/inmunología , Subunidad beta de la Proteína de Unión al Calcio S100/líquido cefalorraquídeo , Subunidad beta de la Proteína de Unión al Calcio S100/inmunología , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo , Factor de Necrosis Tumoral alfa/inmunología , Uganda
17.
J Clin Psychopharmacol ; 36(6): 675-683, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27755221

RESUMEN

To assess the primary metabolite of norepinephrine, 3,4-dihydroxyphenylglycol (DHPG), as a sensitive biomarker for norepinephrine transporter (NET) function and the relationship of DHPG measured peripherally and centrally, NET was antagonized with 80 mg/d atomoxetine for 18 days. Twelve healthy subjects were treated with atomoxetine in an open-label, multiple-dose exploratory study. Plasma atomoxetine reached steady state by day 6, and the pharmacokinetic results demonstrated availability of atomoxetine to the central nervous system. The cerebrospinal fluid (CSF)/plasma ratios of atomoxetine based on area under concentration-time curve from 0 to 12 hours postdose (AUC0-12), maximum concentration (Cmax), and predose were 0.3%, 0.2%, and 11%, respectively. Plasma from atomoxetine-treated subjects (ex vivo) significantly inhibited radioligand binding to human NET (P < 0.001) only 1 hour after dosing. Plasma DHPG and DHPG/norepinephrine (ratio) during repeated posture tests were reduced significantly (P < 0.001) on day 5 and stayed significantly reduced up to 1 day after treatment. In CSF, both DHPG and the ratio were significantly reduced (P < 0.001) on day 18. Urine results showed significant decreases for both DHPG and the ratio (P = 0.010 to P < 0.001). Brain-derived neurotrophic factor in CSF was lesser than the limits of detection. The findings suggest that NET blockade can be assessed with DHPG concentration or with the ratio in plasma, CSF, and urine. The data suggest that DHPG is a useful biomarker to proactively assess the pharmacological activity of compounds intended to inhibit NET activity within the brain. The study shows that CSF is a medium for early identification and quantification of biomarkers useful in assessing novel neuroscience targets.


Asunto(s)
Inhibidores de Captación Adrenérgica/administración & dosificación , Clorhidrato de Atomoxetina/administración & dosificación , Metoxihidroxifenilglicol/análogos & derivados , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/antagonistas & inhibidores , Inhibidores de Captación Adrenérgica/farmacocinética , Inhibidores de Captación Adrenérgica/farmacología , Adulto , Área Bajo la Curva , Clorhidrato de Atomoxetina/farmacocinética , Clorhidrato de Atomoxetina/farmacología , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Femenino , Humanos , Masculino , Metoxihidroxifenilglicol/sangre , Metoxihidroxifenilglicol/líquido cefalorraquídeo , Persona de Mediana Edad , Norepinefrina/metabolismo , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/metabolismo , Adulto Joven
18.
Sci Rep ; 6: 33694, 2016 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-27640722

RESUMEN

Brain-derived neurotrophic factor (BDNF) plays a critical role in cognitive processes including learning and memory. However, it has been difficult to detect BDNF in the brains of behaving animals because of its extremely low concentration, i.e., at the sub-nanogram/mL level. Here, we developed an interdigitated microelectrode (IME) biosensor coated with an anti-BDNF an anti-BDNF antibody in a polydimethylsiloxane (PDMS)-based microfluidic channel chip. This sensor could detect BDNF from microliter volumes of liquid samples even at femtogram/mL concentrations with high selectivity over other growth factors. Using this biosensor, we examined whether BDNF is detectable from periodical collection of cerebrospinal fluid microdialysate, sampled every 10 min from the hippocampus of mice during the context-dependent fear-conditioning test. We found that the IME biosensor could detect a significant increase in BDNF levels after the memory task. This increase in BDNF levels was prevented by gene silencing of BDNF, indicating that the IME biosensor reliably detected BDNF in vivo. We propose that the IME biosensor provides a general-purpose probe for ultrasensitive detection of biomolecules with low abundance in the brains of behaving animals.


Asunto(s)
Técnicas Biosensibles/métodos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Encéfalo/metabolismo , Movimiento , Animales , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Diálisis , Impedancia Eléctrica , Silenciador del Gen , Lentivirus/metabolismo , Ratones , Microelectrodos , ARN Interferente Pequeño/metabolismo
19.
J Alzheimers Dis ; 54(2): 597-613, 2016 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-27567860

RESUMEN

Exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with Alzheimer's disease (AD) risk, while Mn toxicity induces parkinsonism. Mexico City Metropolitan Area (MCMA) children have pre- and postnatal sustained and high exposures to PM2.5, O3, polycyclic aromatic hydrocarbons, and metals. Young MCMA residents exhibit frontal tau hyperphosphorylation and amyloid-ß (Aß)1 - 42 diffuse plaques, and aggregated and hyperphosphorylated α-synuclein in olfactory nerves and key brainstem nuclei. We measured total prion protein (TPrP), total tau (T-tau), tau phosphorylated at threonine 181 (P-Tau), Aß1-42, α-synuclein (t-α-syn and d-α-synuclein), BDNF, insulin, leptin, and/or inflammatory mediators, in 129 normal CSF samples from MCMA and clean air controls. Aß1-42 and BDNF concentrations were significantly lower in MCMA children versus controls (p = 0.005 and 0.02, respectively). TPrP increased with cumulative PM2.5 up to 5 µg/m3 and then decreased, regardless of cumulative value or age (R2 = 0.56). TPrP strongly correlated with T-Tau and P-Tau, while d-α-synuclein showed a significant correlation with TNFα, IL10, and IL6 in MCMA children. Total synuclein showed an increment in childhood years related to cumulated PM2.5, followed by a decrease after age 12 years (R2 = 0.47), while d-α-synuclein exhibited a tendency to increase with cumulated PM2.5 (R2 = 0.30). CSF Aß1-42, BDNF, α-synuclein, and TPrP changes are evolving in young MCMA urbanites historically showing underperformance in cognitive processes, odor identification deficits, downregulation of frontal cellular PrP, and neuropathological AD and PD hallmarks. Neuroprotection of young MCMA residents ought to be a public health priority.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/epidemiología , Enfermedad de Parkinson/líquido cefalorraquídeo , Enfermedad de Parkinson/epidemiología , Material Particulado/efectos adversos , Población Urbana , Adolescente , Adulto , Contaminación del Aire/efectos adversos , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Niño , Ciudades/epidemiología , Humanos , México/epidemiología , Enfermedad de Parkinson/diagnóstico , Fragmentos de Péptidos/líquido cefalorraquídeo , Proyectos Piloto , Estudios Prospectivos , Adulto Joven , alfa-Sinucleína/líquido cefalorraquídeo
20.
Curr Alzheimer Res ; 13(7): 800-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26825093

RESUMEN

The discovery of biomarkers for the onset of Alzheimer's disease (AD) is essential for disease modification strategies. To date, AD biomarker studies have focused on brain imaging and cerebrospinal fluid (CSF) changes in amyloid- ß (Aß) peptide and tau proteins. While reliable to an extent, this panel could be improved by the inclusion of novel biomarkers that optimize sensitivity and specificity. In this study, we determined whether CSF levels of the nerve growth factor (NGF) precursor protein, proNGF, increased during the progression of AD, mirroring its up regulation in postmortem brain samples of people who died with a clinical diagnosis of mild cognitive impairment (MCI) or AD. Immunoblot analysis was performed on ventricular CSF harvested from participants in the Rush Religious Orders Study with an antemortem clinical diagnosis of no cognitive impairment (NCI), amnestic MCI (aMCI, a putative prodromal AD stage), or mild/moderate AD. ProNGF levels were increased 55% in aMCI and 70% in AD compared to NCI. Increasing CSF proNGF levels correlated with impairment on cognitive test scores. In a complementary study, we found that proNGF was significantly increased by 30% in lumbar CSF samples derived from patients with a clinical dementia rating (CDR) of 0.5 or 1 compared to those with a CDR = 0. Notably, proNGF/Aß1-42 levels were 50% higher in CDR 0.5 and CDR 1 compared to CDR 0 controls. By contrast, ELISA measurements of CSF brain-derived neurotrophic factor (BDNF) did not distinguish aMCI from NCI. Taken together, these results suggest that proNGF protein levels may augment the diagnostic accuracy of currently used CSF biomarker panels.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Factor de Crecimiento Nervioso/líquido cefalorraquídeo , Precursores de Proteínas/líquido cefalorraquídeo , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Disfunción Cognitiva/líquido cefalorraquídeo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Escala del Estado Mental , Persona de Mediana Edad
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...