Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 10 de 10
Filter
1.
Madrid; REDETS-ISCIII; 2023.
Non-conventional in Spanish | BRISA/RedTESA | ID: biblio-1571666

ABSTRACT

INTRODUCCIÓN La enfermedad de Alzheimer (EA) es la enfermedad neurodegerativa depen diente de la edad más frecuente. Se caracteriza clínicamente por causar una demen cia e histopatológicamente por la aparición de placas de amiloide y de ovillos neu rofibrilares (NFT por sus siglas en inglés), producidos por el depósito extracelular de beta amiloide (Aß) y la agregación intracelular de proteína tau hiperfosforilada (p-tau). Se puede considerar la EA como un continuo que comprende la transición desde una fase preclínica asintomática, en la que se pueden detectar cambios pato lógicos en el cerebro mediante pruebas de imagen y análisis en líquido cefalorraquí deo (LCR), a una fase prodrómica de deterioro cognitivo leve (DCL) hasta alcan zar la fase demencia establecida. El DCL representa un estado intermedio entre los cambios cognitivos del envejecimiento y la demencia temprana. En la actualidad, el diagnóstico de la EA se basa en su presentación clínica, apoyándose también en la realización de determinados exámenes y test neuropsi cológicos. El diagnóstico de certeza se basa en la aplicación de determinados


Subject(s)
tau Proteins/blood , Alzheimer Disease/diagnosis , Effectiveness , Biomarkers
2.
J Alzheimers Dis ; 82(s1): S271-S281, 2021.
Article in English | MEDLINE | ID: mdl-34151786

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) causes memory deficit and alterations in other cognitive functions, mainly in adults over 60 years of age. As the diagnosis confirmation is performed by a postmortem neuropathological examination of the brain, this disease can be confused with other types of dementia at early stages. About 860,000 Mexicans are affected by dementia, most of them with insufficient access to adequate comprehensive health care services. Plasma biomarkers could be a rapid option for early diagnosis of the disease. OBJECTIVE: This study aimed to analyze some plasma biomarkers (amyloid-ß, tau, and lipids) in Mexican AD patients and control subjects with no associated neurodegenerative diseases. METHODS: Plasma amyloid-ß peptides (Aß40 and Aß42), total and phosphorylated tau protein (T-tau and P-tau), and cholesterol and triglyceride levels were quantified by enzyme-linked immunosorbent assay in AD patients and control subjects. RESULTS: In Mexican AD patients, we found significantly lower levels of Aß42 (p < 0.05) compared to the control group. In contrast, significantly higher levels of P-tau (p < 0.05) and triglycerides (p < 0.05) were observed in AD patients compared to controls. Furthermore, a significant correlation was found between the severity of dementia and plasma P-tau levels, Aß42/Aß40 and P-tau/T-tau ratios, and triglycerides concentrations. This correlation increased gradually with cognitive decline. CONCLUSION: The detection of these plasma biomarkers is an initial step in searching for a timely, less invasive, and cost-efficient diagnosis in Mexicans.


Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/epidemiology , Amyloid beta-Peptides/blood , tau Proteins/blood , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Biomarkers/blood , Female , Humans , Male , Mexico/epidemiology , Middle Aged
3.
J Alzheimers Dis ; 77(2): 877-883, 2020.
Article in English | MEDLINE | ID: mdl-32741827

ABSTRACT

BACKGROUND: A major drawback in Alzheimer's disease (AD) is the lack of validated biomarkers for routine clinical diagnostic. We have reported earlier a novel blood biomarker, named Alz-tau®, based on variants of platelet tau. This marker evaluates the ratio of high molecular weight tau (HMWtau) and the low molecular weight (LMWtau) tau. OBJECTIVE: To analyze a potential novel source of antigen for Alz-tau®, plasma tau, detected by immunoreactivity with the novel monoclonal antibody, tau51. METHODS: We evaluated tau variants in plasma precipitated with ammonium sulfate from 36 AD patients and 15 control subjects by western blot with this novel monoclonal antibody. RESULTS: The HMW/LMWtau ratio was statistically different between AD patients and controls. CONCLUSIONS: Plasma tau variants are suitable to be considered as a novel antigen source for the Alz-tau® biomarker for AD.


Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/diagnosis , Antibodies, Monoclonal/blood , Genetic Variation/physiology , tau Proteins/blood , Aged , Aged, 80 and over , Alzheimer Disease/genetics , Antibodies, Monoclonal/genetics , Biomarkers/blood , Female , Humans , Male , Middle Aged , tau Proteins/genetics
4.
J Alzheimers Dis ; 67(4): 1181-1186, 2019.
Article in English | MEDLINE | ID: mdl-30775977

ABSTRACT

The establishment of a molecular biomarker for early detection of Alzheimer's disease (AD) is critical for diagnosis and follow up of patients, and as a quantitative parameter in the evaluation of potential new drugs to control AD. A list of blood biomarkers has been reported but none has been validated for the Alzheimer's clinic. The changes in hyperphosphorylated tau and amyloid peptide in the cerebrospinal fluid is currently used as a tool in the clinics and for research purposes, but this method is highly invasive. Recently, we reported a non-invasive and reliable blood biomarker that correlates the increase in the ratio of heavy tau (HMWtau) and the low molecular weight tau (LMWtau) in human platelets and the decrease in the brain volume as measured by structural MRI. This molecular marker has been named Alz-tau®. Beyond the clinical trials developed with a Latin American population, the present study focuses on an evaluation of this biomarker in a Caucasian population. We examined 36 AD patients and 15 cognitively normal subjects recruited in Barcelona, Spain. Tau levels in platelets were determined by immunoreactivity and the cognitive status by using GDS and MMSE neuropsychological tests. The HMW/LMW tau ratio was statistically different between controls and AD patients. A high correlation was found between the increase in MMSE scores and HMW/LMW tau ratio. This study showed that this ratio is significantly higher in AD patients than controls. Moreover, this study on a peripheral marker of AD is valuable to understanding the AD pathogenesis.


Subject(s)
Alzheimer Disease/blood , Mental Status and Dementia Tests , tau Proteins , Aged , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Biomarkers/blood , Blood Platelets/metabolism , Chile , Correlation of Data , Early Diagnosis , Female , Humans , Male , Molecular Weight , Reproducibility of Results , White People , tau Proteins/blood , tau Proteins/chemistry
5.
Biomark Med ; 12(7): 717-726, 2018 07.
Article in English | MEDLINE | ID: mdl-29865854

ABSTRACT

AIM: Determine if serum levels of tau and BDNF can be used as severity biomarkers in multiple sclerosis (MS). PATIENTS & METHODS: Subjects with MS, older than 18 and younger than 55 years old were included; 74 patients with a diagnosis of relapsing-remitting MS, 11 with secondary-progressive MS, and 88 controls were included. Total tau and BDNF were measured by Western blot. RESULTS: Increased tau and decreased BDNF in MS patients compared with controls was found. Total-tau has a peak in relapsing-remitting MS, the second decile of the multiple sclerosis severity score, and in the lowest expanded disability status scale and is no different than controls for secondary-progressive MS patients and the most severe cases of MS. CONCLUSION: BDNF is a good biomarker for diagnosis of MS but not for severity or progression. Tau appears to have a more active role in the progression of MS.


Subject(s)
Brain-Derived Neurotrophic Factor/blood , Multiple Sclerosis/blood , Severity of Illness Index , tau Proteins/blood , Adult , Biomarkers/blood , Case-Control Studies , Female , Humans , Male , Risk
6.
J Pediatr ; 194: 67-75.e1, 2018 03.
Article in English | MEDLINE | ID: mdl-29478510

ABSTRACT

OBJECTIVES: To evaluate plasma brain specific proteins and cytokines as biomarkers of brain injury in newborns with hypoxic-ischemic encephalopathy (HIE) and, secondarily, to assess the effect of erythropoietin (Epo) treatment on the relationship between biomarkers and outcomes. STUDY DESIGN: A study of candidate brain injury biomarkers was conducted in the context of a phase II multicenter randomized trial evaluating Epo for neuroprotection in HIE. Plasma was collected at baseline (<24 hours) and on day 5. Brain injury was assessed by magnetic resonance imaging (MRI) and neurodevelopmental assessments at 1 year. The relationships between Epo, brain-specific proteins (S100B, ubiquitin carboxy-terminal hydrolase-L1 [UCH-L1], total Tau, neuron specific enolase), cytokines (interleukin [IL]-1ß, IL-6, IL-8, IL-10, IL-12P70, IL-13, interferon-gamma [IFN-γ], tumor necrosis factor alpha [TNF-α], brain-derived neurotrophic factor [BDNF], monocyte chemoattractant protein-1), and brain injury were assessed. RESULTS: In 50 newborns with encephalopathy, elevated baseline S100B, Tau, UCH-L1, IL-1ß, IL-6, IL-8, IL-10, IL-13, TNF-α, and IFN-γ levels were associated with increasing brain injury severity by MRI. Higher baseline Tau and lower day 5 BDNF were associated with worse 1 year outcomes. No statistically significant evidence of Epo treatment modification on biomarkers was detected in this small cohort. CONCLUSIONS: Elevated plasma brain-specific proteins and cytokine levels in the first 24 hours of life are associated with worse brain injury by MRI in newborns with HIE. Only Tau and BDNF levels were found to be related to neurodevelopmental outcomes. The effect of Epo treatment on the relationships between biomarkers and brain injury in HIE requires further study. TRIAL REGISTRATION: ClinicalTrials.gov: 01913340.


Subject(s)
Brain Injuries/blood , Hypoxia-Ischemia, Brain/blood , Biomarkers/blood , Brain Injuries/diagnostic imaging , Brain Injuries/etiology , Brain-Derived Neurotrophic Factor/blood , Cytokines/blood , Erythropoietin/therapeutic use , Humans , Hypoxia-Ischemia, Brain/complications , Hypoxia-Ischemia, Brain/drug therapy , Infant, Newborn , Magnetic Resonance Imaging , tau Proteins/blood
7.
J Neurovirol ; 24(1): 28-40, 2018 02.
Article in English | MEDLINE | ID: mdl-29063514

ABSTRACT

Based on prior reports that the HIV-1 Tat protein modulates amyloid-beta (Aß) metabolism, this study aimed to compare CSF neural injury biomarkers between 27 patients with HIV subtype B, 26 patients with HIV subtype C, 18 healthy HIV-negative controls, and 24 patients with Alzheimer's disease (AD). Immunoassays were used to measure soluble amyloid precursor protein α and ß (sAPPα, sAPPß), Aß oligomers 38, 40, 42, and Aß-total; phosphorylated tau (P-tau181), and total tau (T-tau). Comparisons between HIV(+) and HIV(-) (including AD) were adjusted by linear regression for gender and age; HIV subtype comparisons were adjusted for nadir CD4 and plasma viral load suppression. The p values were corrected for multiple testing with the Benjamini-Hochberg procedure. CSF Aß-42 and Hulstaert (P-tau181) index were lower in HIV1-C than B (p = 0.03, and 0.049 respectively); subtypes did not differ on other CSF biomarkers or ratios. Compared to AD, HIV(+) had lower CSF levels of T-tau, P-tau181 (p < 0.001), and sAPPα (p = 0.041); HIV(+) had higher CSF Aß-42 (p = 0.002) and higher CSF indexes: [Aß-42/(240 + 1.18 T-tau)], P-tau181/Aß-42, T-tau/Aß-42, P-tau181/T-tau, sAPPα/ß (all p ≤ 0.01) than AD. Compared to HIV(-), HIV(+) had lower CSF Aß-42, and T-tau (all p ≤ 0.004). As conclusion, amyloid metabolism was influenced by HIV infection in a subtype-dependent manner. Aß-42 levels were lower in HIV1-C than B, suggesting that there may be greater deposition of Aß-42 in HIV1-C. These findings are supported by CSF Hulstaert (P-tau181) index. Differences between HIV and AD in the patterns of Aß and Tau biomarkers suggest that CNS HIV infection and AD may not share some of same mechanisms of neuronal injury.


Subject(s)
Alzheimer Disease/cerebrospinal fluid , Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Protein Precursor/cerebrospinal fluid , HIV Infections/cerebrospinal fluid , HIV-1/classification , tau Proteins/cerebrospinal fluid , Adult , Aged , Alzheimer Disease/blood , Alzheimer Disease/immunology , Alzheimer Disease/pathology , Amyloid beta-Peptides/blood , Amyloid beta-Protein Precursor/blood , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Brain/metabolism , Brain/pathology , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/virology , Cross-Sectional Studies , Female , Genotype , HIV Infections/blood , HIV Infections/immunology , HIV Infections/pathology , HIV-1/genetics , Humans , Male , Middle Aged , Neurons/metabolism , Neurons/pathology , Viral Load , tau Proteins/blood
8.
J Alzheimers Dis ; 55(4): 1595-1603, 2017.
Article in English | MEDLINE | ID: mdl-27911301

ABSTRACT

BACKGROUND: Intracellular neurofibrillary tangles are part of the core pathology of Alzheimer's disease (AD), which are mainly composed of hyperphosphorylated tau protein. OBJECTIVES: The purpose of this study is to determine whether high molecular weight (HMW) or low molecular weight (LMW) tau protein levels, as well as the ratio HMW/LMW, present in platelets correlates with brain magnetic resonance imaging (MRI) structural changes in normal and cognitively impaired subjects. METHODS: We examined 53 AD patients and 37 cognitively normal subjects recruited from two Memory Clinics at the Universidad de Chile. Tau levels in platelets were determined by immunoreactivity and the MRI scans were analyzed using voxel-based morphometry in 41 AD patients. RESULTS: The HMW/LMW tau ratio was statistically different between controls and AD patients, and no associations were noted between HMW or LMW tau and MRI structures. In a multivariate analysis controlled for age and education level, the HMW/LMW tau ratio was associated with reduced volume in the left medial and right anterior cingulate gyri, right cerebellum, right thalamus (pulvinar), left frontal cortex, and right parahippocampal region. CONCLUSIONS: This exploratory study showed that HMW/LMW tau ratio is significantly higher in AD patients than control subjects, and that it is associated with specific brain regions atrophy. Determination of peripheral markers of AD pathology can help understanding the pathophysiology of neurodegeneration in AD.


Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/complications , Blood Platelets/metabolism , Brain/pathology , tau Proteins/blood , Aged , Aged, 80 and over , Alzheimer Disease/diagnostic imaging , Atrophy/diagnostic imaging , Atrophy/etiology , Brain/diagnostic imaging , Chile , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Mental Status Schedule , Middle Aged
9.
Arch Med Res ; 43(8): 663-6, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23142260

ABSTRACT

Alzheimer's disease (AD) diagnosis still depends on the triad of clinical, imaging and neuropsychological testing. The development of accurate, easy to use and inexpensive biological markers for AD is a long-standing aspiration for researchers and the medical community. Here we describe some of the recent advances in the field of biomarkers, both in cerebrospinal fluid (CSF) and in peripheral blood.


Subject(s)
Alzheimer Disease/diagnosis , Early Diagnosis , Alzheimer Disease/blood , Alzheimer Disease/cerebrospinal fluid , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Blood Platelets/metabolism , Humans , Sensitivity and Specificity , tau Proteins/blood
10.
J Alzheimers Dis ; 31(1): 65-9, 2012.
Article in English | MEDLINE | ID: mdl-22495344

ABSTRACT

Platelets are major reservoirs of circulating amyloid-ß and amyloid-ß protein precursor (AßPP) and have been postulated as a reliable source for biological markers of Alzheimer's disease (AD). We have recently demonstrated that tau is also present in platelets, and that there are differences in the electrophoretic patterns of platelet tau forms in AD subjects with respect to controls. Here, we demonstrate that modifications in platelet tau forms occur independently of age in a broad population of 104 neurologically healthy individuals. More interesting, a strong correlation of platelet markers with the degree of cognitive impairment was evidenced in a group of 47 AD patients in comparison with 19 cognitive healthy subjects. In our series, platelet tau forms ratio had a sensitivity of 75.7% and specificity of 73.7%, respectively. We also found that platelet tau displays a significantly higher correlation with the presence of AD than the analyses of platelet AßPP.


Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/complications , Cognition Disorders/blood , Cognition Disorders/etiology , Statistics as Topic , tau Proteins/blood , Aged , Aged, 80 and over , Analysis of Variance , Female , Humans , Male , Mental Status Schedule , Middle Aged , ROC Curve
SELECTION OF CITATIONS
SEARCH DETAIL