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OBJECTIVES: Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting approximately 55 million individuals globally. Diagnosis typically occurs in advanced stages, and there are limited options for reversing symptoms. Preventive strategies are, therefore, crucial. Time Restricted Eating (TRE) or Time Restricted Feeding (TRF) is one such strategy. Here we review recent research on AD and TRE/TRF in addition to AD biomarkers and gut microbiota. METHODS: A comprehensive review of recent studies was conducted to assess the impact of TRE/TRF on AD-related outcomes. This includes the analysis of how TRE/TRF influences circadian rhythms, beta-amyloid 42 (Aß42), pro-inflammatory cytokines levels, and gut microbiota composition. RESULTS: TRE/TRF impacts circadian rhythms and can influence cognitive performance as observed in AD. It lowers beta-amyloid 42 deposition in the brain, a key AD biomarker, and reduces pro-ininflammatory cytokines. The gut microbiome has emerged as a modifiable factor in AD treatment. TRE/TRF changes the structure and composition of the gut microbiota, leading to increased diversity and a decrease in harmful bacteria. DISCUSSION: These findings underscore the potential of TRE/TRF as a preventive strategy for AD. By reducing Aß42 plaques, modulating pro-inflammatory cytokines, and altering gut microbiota composition, TRE/TRF may slow the progression of AD. Further research is needed to confirm these effects and to understand the mechanisms involved. This review highlights TRE/TRF as a promising non-pharmacological intervention in the fight against AD.
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We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in â¼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P < 1 × 10-3), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases.
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Enfermedad de la Arteria Coronaria , Enfermedad de la Arteria Coronaria/genética , Sitios Genéticos , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Homeostasis , Humanos , Lipidómica , Lípidos , Polimorfismo de Nucleótido SimpleRESUMEN
Previous studies have indicated that physical activity may be beneficial in reducing the risk for Alzheimer's disease (AD), although the underlying mechanisms are not fully understood. The goal of this study was to evaluate the relationship between habitual physical activity levels and brain amyloid deposition and AD-related blood biomarkers (i.e., measured using a novel high-performance mass spectrometry-based assay), in apolipoprotein E (APOE) ε4 carriers and noncarriers. We evaluated 143 cognitively normal older adults, all of whom had brain amyloid deposition assessed using positron emission tomography and had their physical activity levels measured using the International Physical Activity Questionnaire (IPAQ). We observed an inverse correlation between brain amyloidosis and plasma beta-amyloid (Aß)1-42 but found no association between brain amyloid and plasma Aß1-40 and amyloid precursor protein (APP)669-711. Additionally, higher levels of physical activity were associated with lower plasma Aß1-40, Aß1-42, and APP669-711 levels in APOE ε4 noncarriers. The ratios of Aß1-40/Aß1-42 and APP669-711/Aß1-42, which have been associated with higher brain amyloidosis in previous studies, differed between APOE ε4 carriers and non-carriers. Taken together, these data indicate a complex relationship between physical activity and brain amyloid deposition and potential blood-based AD biomarkers in cognitively normal older adults. In addition, the role of APOE ε4 is still unclear, and more studies are necessary to bring further clarification.
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INTRODUCTION: The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late-onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood. METHODS: We performed lipidomic analysis on three independent cohorts (the Australian Imaging, Biomarkers and Lifestyle [AIBL] flagship study, n = 1087; the Alzheimer's Disease Neuroimaging Initiative [ADNI] 1 study, n = 819; and the Busselton Health Study [BHS], n = 4384), and we defined associations between APOE ε2 and ε4 and 569 plasma/serum lipid species. Mediation analysis defined the proportion of the treatment effect of the APOE genotype mediated by plasma/serum lipid species. RESULTS: A total of 237 and 104 lipid species were associated with APOE ε2 and ε4, respectively. Of these 68 (ε2) and 24 (ε4) were associated with prevalent Alzheimer's disease. Individual lipid species or lipidomic models of APOE genotypes mediated up to 30% and 10% of APOE ε2 and ε4 treatment effect, respectively. DISCUSSION: Plasma lipid species mediate the treatment effect of APOE genotypes on Alzheimer's disease and as such represent a potential therapeutic target.
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Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/genética , Apolipoproteína E2/genética , Australia , Apolipoproteínas E/genética , Genotipo , Estudios de Cohortes , Apolipoproteína E4/genéticaRESUMEN
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently has no cure. Identifying biochemical changes associated with neurodegeneration prior to symptom onset, will provide insight into the biological mechanisms associated with neurodegenerative processes, that may also aid in identifying potential drug targets. The current study therefore investigated associations between plasma neurofilament light chain (NF-L), a marker of neurodegeneration, with plasma metabolites that are products of various cellular processes. Plasma NF-L, measured by ultrasensitive Single molecule array (Simoa) technology (Quanterix) and plasma metabolites, measured by mass-spectrometry (AbsoluteIDQ® p400HR kit, BIOCRATES), were assessed in the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohort comprising 100 cognitively normal older adults. Metabolites belonging to biogenic amine (creatinine, symmetric dimethylarginine, asymmetric dimethylarginine; ADMA, kynurenine, trans-4-hydroxyproline), amino acid (citrulline, proline, arginine, asparagine, phenylalanine, threonine) and acylcarnitine classes were observed to have positive correlations with plasma NF-L, suggesting a link between neurodegeneration and biological pathways associated with neurotransmitter regulation, nitric oxide homoeostasis, inflammation and mitochondrial function. Additionally, after stratifying participants based on low/high brain amyloid-ß load (Aß ±) assessed by positron emission tomography, while creatinine, SDMA and citrulline correlated with NF-L in both Aß- and Aß+ groups, ADMA, proline, arginine, asparagine, phenylalanine and acylcarnitine species correlated with NF-L only in the Aß+ group after adjusting for confounding variables, suggesting that the association of these metabolites with neurodegeneration may be relevant to AD-related neuropathology. Metabolites identified to be associated with plasma NF-L may have the potential to serve as prognostic markers for neurodegenerative diseases, however, further studies are required to validate the current findings in an independent cohort, both cross-sectionally and longitudinally.
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Enfermedades Neurodegenerativas/sangre , Anciano , Anciano de 80 o más Años , Péptidos beta-Amiloides/análisis , Aminas Biogénicas/metabolismo , Biomarcadores/análisis , Cognición , Estudios de Cohortes , Encefalitis/metabolismo , Femenino , Humanos , Masculino , Espectrometría de Masas/métodos , Mitocondrias/metabolismo , Enfermedades Neurodegenerativas/diagnóstico , Enfermedades Neurodegenerativas/psicología , Proteínas de Neurofilamentos/análisis , Neurotransmisores/metabolismo , Óxido Nítrico/metabolismo , Tomografía de Emisión de Positrones , PronósticoRESUMEN
BACKGROUND: Cerebral amyloid angiopathy (CAA) is one of the major causes of intracerebral hemorrhage and vascular dementia in older adults. Early diagnosis will provide clinicians with an opportunity to intervene early with suitable strategies, highlighting the importance of pre-symptomatic CAA biomarkers. OBJECTIVE: Investigation of pre-symptomatic CAA related blood metabolite alterations in Dutch-type hereditary CAA mutation carriers (D-CAA MCs). METHODS: Plasma metabolites were measured using mass-spectrometry (AbsoluteIDQ® p400 HR kit) and were compared between pre-symptomatic D-CAA MCs (n = 9) and non-carriers (D-CAA NCs, n = 8) from the same pedigree. Metabolites that survived correction for multiple comparisons were further compared between D-CAA MCs and additional control groups (cognitively unimpaired adults). RESULTS: 275 metabolites were measured in the plasma, 22 of which were observed to be significantly lower in theD-CAAMCs compared to D-CAA NCs, following adjustment for potential confounding factors age, sex, and APOE ε4 (p < 00.05). After adjusting for multiple comparisons, only spermidine remained significantly lower in theD-CAAMCscompared to theD-CAA NCs (p < 0.00018). Plasma spermidine was also significantly lower in D-CAA MCs compared to the cognitively unimpaired young adult and older adult groups (p < 0.01). Spermidinewas also observed to correlate with CSF Aß40 (rs = 0.621, p = 0.024), CSF Aß42 (rs = 0.714, p = 0.006), and brain Aß load (rs = -0.527, p = 0.030). CONCLUSION: The current study provides pilot data on D-CAA linked metabolite signals, that also associated with Aß neuropathology and are involved in several biological pathways that have previously been linked to neurodegeneration and dementia.
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Angiopatía Amiloide Cerebral Familiar/sangre , Adulto , Enfermedades Asintomáticas , Biomarcadores/sangre , Estudios de Casos y Controles , Angiopatía Amiloide Cerebral Familiar/genética , Angiopatía Amiloide Cerebral Familiar/metabolismo , Femenino , Heterocigoto , Humanos , Masculino , Espectrometría de Masas , Pruebas de Estado Mental y Demencia , Metabolómica , Neuroimagen , Linaje , Placa Amiloide/diagnóstico por imagen , Tomografía de Emisión de Positrones , Espermidina/sangre , Espermidina/metabolismoRESUMEN
The Itapemirim River is considered one of the most important water resources in the state of Espírito Santo, Brazil. However, environmental problems due to continuous anthropogenic contamination are threatening its potential use. This study assessed water quality by analyzing abiotic and toxicogenetic aspects of the water from four stations along the river. Samples were collected in both dry and rainy seasons. Most of the abiotic variables were below the threshold established by CONAMA Resolution No. 357/2005, and so were most of the metals. However, Al and Cu contents were above those allowed by legislation, ranging from 0.2 to 0.9 mg/L. Regarding toxicogenetic aspects, genotoxic effects were observed in meristematic cells of Allium cepa, in micronucleus test and comet assay of Oreochromis niloticus, and CHO-K1 cells. Mutagenic effects were significant at RI 02 (0.34), RI 03 (0.46), and RI 04 (0.12) stations on the first campaign in A. cepa F1 cells, compared to the negative control (0.0). The second campaign revealed the same results, but with the addition of samples from RI 01 (0.17) and RI 03 (0.18) showing mutagenicity in the micronucleus test with fish erythrocytes when compared to the negative control (0.3). Essentially, all the samples evaluated in both campaigns showed damage in A. cepa, O. niloticus, and CHO-K1 cells, thus demonstrating that the water quality of the Itapemirim River is compromised and requires action plans for its recovery.
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Ríos , Contaminantes Químicos del Agua , Animales , Brasil , Daño del ADN , Monitoreo del Ambiente , Pruebas de Micronúcleos , Toxicogenética , Agua , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidadRESUMEN
Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer's disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation. In this study we examined peripheral samples of two cohorts (AIBL, n = 1112 and ADNI, n = 800). We are able to identify concordant peripheral signatures associated with prevalent AD arising from lipid pathways including; ether lipids, sphingolipids (notably GM3 gangliosides) and lipid classes previously associated with cardiometabolic disease (phosphatidylethanolamine and triglycerides). We subsequently identified similar lipid signatures in both cohorts with future disease. Lastly, we developed multivariate lipid models that improved classification and prediction. Our results provide a holistic view between the lipidome and AD using a comprehensive approach, providing targets for further mechanistic investigation.
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Enfermedad de Alzheimer/metabolismo , Lipidómica , Lípidos/sangre , Biomarcadores/sangre , Estudios de Cohortes , Simulación por Computador , Humanos , Metabolismo de los Lípidos , MetabolómicaRESUMEN
BACKGROUND: The link between cholesterol and Alzheimer's disease (AD) has received much attention, as evidence suggests high levels of cholesterol might be an AD risk factor. The carriage of cholesterol and lipids through the body is mediated via lipoproteins, some of which, particularly apolipoprotein E (ApoE), are intimately linked with AD. In humans, high density lipoprotein (HDL) is regarded as a "good" lipid complex due to its ability to enable clearance of excess cholesterol via 'cholesterol reverse transport', although its activities in the pathogenesis of AD are poorly understood. There are several subclasses of HDL; these range from the newly formed small HDL, to much larger HDL. OBJECTIVE: We examined the major subclasses of HDL in healthy controls, mild cognitively impaired, and AD patients who were not taking statins to determine whether there were HDL profile differences between the groups, and whether HDL subclass levels correlated with plasma amyloid-ß (Aß) levels or brain Aß deposition. METHODS: Samples from AIBL cohort were used in this study. HDL subclass levels were assessed by Lipoprint while Aß1-42 levels were assessed by ELISA. Brain Aß deposition was assessed by PET scan. Statistical analysis was performed using parametric and non-parametric tests. RESULTS: We found that small HDL subclass is reduced in AD patients and it correlates with cognitive performance while plasma Aß concentrations do not correlate with lipid profile or HDL subfraction levels. CONCLUSION: Our data indicate that AD patients exhibit altered plasma HDL profile and that HDL subclasses correlate with cognitive performances.
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Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/psicología , Péptidos beta-Amiloides/sangre , Cognición/fisiología , Lipoproteínas HDL/sangre , Fragmentos de Péptidos/sangre , Desempeño Psicomotor/fisiología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/genética , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Humanos , Lipoproteínas HDL/genética , Masculino , Fragmentos de Péptidos/genéticaRESUMEN
BACKGROUND: Lipid metabolism is altered in Alzheimer's disease (AD); however, the relationship between AD risk factors (age, APOEÉ4, and gender) and lipid metabolism is not well defined. OBJECTIVE: We investigated whether altered lipid metabolism associated with increased age, gender, and APOE status may contribute to the development of AD by examining these risk factors in healthy controls and also clinically diagnosed AD individuals. METHODS: We performed plasma lipidomic profiling (582 lipid species) of the Australian Imaging, Biomarkers and Lifestyle flagship study of aging cohort (AIBL) using liquid chromatography-mass spectrometry. Linear regression and interaction analysis were used to explore the relationship between risk factors and plasma lipid species. RESULTS: We observed strong associations between plasma lipid species with gender and increasing age in cognitively normal individuals. However, APOEÉ4 was relatively weakly associated with plasma lipid species. Interaction analysis identified differential associations of sphingolipids and polyunsaturated fatty acid esterified lipid species with AD based on age and gender, respectively. These data indicate that the risk associated with age, gender, and APOEÉ4 may, in part, be mediated by changes in lipid metabolism. CONCLUSION: This study extends our existing knowledge of the relationship between the lipidome and AD and highlights the complexity of the relationships between lipid metabolism and AD at different ages and between men and women. This has important implications for how we assess AD risk and also for potential therapeutic strategies involving modulation of lipid metabolic pathways.
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Enfermedad de Alzheimer/sangre , Metabolismo de los Lípidos/fisiología , Lipidómica/métodos , Lípidos/sangre , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Australia/epidemiología , Biomarcadores/sangre , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Factores de Riesgo , Factores SexualesRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and neuropathological features, including abnormal deposition of amyloid-ß (Aß) peptides, intracellular neurofibrillary tangles, and neuronal death. Identifying therapeutics which can reduce memory deficits at an early stage of the disease has the advantage of slowing or even reversing disease progression before irreversible brain damage has occurred. Consequently, in this study, we investigated the ability of the histone deacetylase inhibitor sodium butyrate (NaB) to attenuate memory deficits in the 5xFAD mouse model of AD following a 12-week feeding regimen. 5xFAD mice demonstrate a unique time course of Aß pathology, developing Aß plaques as early as 2 months. Male mice were assigned to either a control diet or a NaB-supplemented diet which was administered at either 5âmg/kg/day, or 15âmg/kg/day for 12 weeks (each group, Nâ=â15). Supplementation commenced at an early disease stage (8-10 weeks of age). Behavioral testing (contextual and cued fear conditioning) was undertaken, and brain Aß levels measured, at the end of the 12-week intervention. NaB had profound effects on Aß levels and on associative learning and cognitive functioning. A 40% reduction in brain Aß levels and a 25% increase in fear response in both the cued and contextual testing was observed in the NaB-treated animals compared to the control group. These findings suggest that NaB warrants further investigation as a potential therapeutic agent in the treatment of cognitive deficits associated with early stages of AD.
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Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Química Encefálica/efectos de los fármacos , Ácido Butírico/farmacología , Memoria/efectos de los fármacos , Nootrópicos/farmacología , Enfermedad de Alzheimer/genética , Animales , Señales (Psicología) , Dieta , Miedo/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones TransgénicosRESUMEN
The heat shock response involved in protein misfolding is linked to the formation of toxic immunogenic proteins with heat shock proteins (HSP) as regulators of amyloid beta aggregation. The defective amyloid beta trafficking between different intracellular compartments is now relevant to HSPs and autoimmunity. Overnutrition, temperature dysregulation, and stress repress the heat shock gene Sirtuin 1 with the induction of HSP regulated amyloid beta aggregation involved in the autoimmune response. Defective circadian rhythm alterations are connected to inactivation of the peripheral sink amyloid beta clearance pathway and related to insulin resistance, protein aggregation, and autoimmune disease in non-alcoholic fatty liver disease (NAFLD) and various neurodegenerative diseases such as Alzheimer's disease. Nutritional therapy is critical to prevent immunosenescence, and plasma Sirtuin 1 levels should be determined to reverse, stabilize, and prevent protein aggregation with relevance to mitochondrial apoptosis and programmed cell death in chronic diseases.
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Worldwide there are over 46 million people living with dementia, and this number is expected to double every 20 years reaching about 131 million by 2050. The cost to the community and government health systems, as well as the stress on families and carers is incalculable. Over three decades of research into this disease have been undertaken by several research groups in Australia, including work by our original research group in Western Australia which was involved in the discovery and sequencing of the amyloid-ß peptide (also known as Aß or A4 peptide) extracted from cerebral amyloid plaques. This review discusses the journey from the discovery of the Aß peptide in Alzheimer's disease (AD) brain to the establishment of pre-clinical AD using PET amyloid tracers, a method now serving as the gold standard for developing peripheral diagnostic approaches in the blood and the eye. The latter developments for early diagnosis have been largely achieved through the establishment of the Australian Imaging Biomarker and Lifestyle research group that has followed 1,100 Australians for 11 years. AIBL has also been instrumental in providing insight into the role of the major genetic risk factor apolipoprotein E É4, as well as better understanding the role of lifestyle factors particularly diet, physical activity and sleep to cognitive decline and the accumulation of cerebral Aß.
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Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/prevención & control , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/metabolismo , Proteínas Amiloidogénicas/metabolismo , Animales , Australia/epidemiología , Biomarcadores/metabolismo , Humanos , Estrés Oxidativo/fisiologíaRESUMEN
Biological process treatment of landfill leachate produces a significant amount of sludge, characterized by high levels of organic matter from which humic acids are known to activate several enzymes of energy metabolism, stimulating plant growth. This study aimed to characterize humic acids extracted from landfill sludge and assess the effects on plants exposed to different concentrations (0.5, 1, 2 and 4 mM C L-1) by chemical and biological analysis, to elucidate the influence of such organic material and minimize potential risks of using sludge in natura. Landfill humic acids showed high carbon and nitrogen levels, which may represent an important source of nutrients for plants. Biochemical analysis demonstrated an increase of enzyme activity, especially H+-ATPase in 2 mM C L-1 landfill humic acid. Additionally, cytogenetic alterations were observed in meristematic and F1 cells, through nuclear abnormalities and micronuclei. Multivariate statistical analysis provided integration of physical, chemical and biological data. Despite all the nutritional benefits of humic acids and their activation of plant antioxidant systems, the observed biological effects showed concerning levels of mutagenicity.
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Sustancias Húmicas/análisis , Desarrollo de la Planta/efectos de los fármacos , Instalaciones de Eliminación de Residuos , Adenosina Trifosfatasas/análisis , Carbono/análisis , Análisis Citogenético , Sustancias Húmicas/toxicidad , Mutagénesis , Nitrógeno/análisis , Aguas del Alcantarillado , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidadRESUMEN
Purpose/Aim of the study: Poor cardiovascular health, including obesity and altered lipid profiles at mid-life, are linked to increased risk of Alzheimer's disease (AD). The biological mechanisms linking cardiovascular health and cognitive function are unclear though are likely to be multifactorial. This study examined the association between various lipoproteins and cognitive functioning in ageing women. MATERIALS AND METHODS: We investigated the relationship between readily available biomarkers (i.e. serum lipoprotein) and cognitive decline in domains associated with increased risk of AD (e.g. episodic verbal memory performance and subjective memory complaint). We report cross-sectional data investigating the relationship between serum total cholesterol, triglycerides, high-density lipoprotein (HDL-C) and low-density lipoprotein with verbal memory and learning ability in 130 women with and without memory complaints (n = 71 and 59, respectively) drawn from a study investigating cognitively healthy Western Australians (average age 62.5 years old). RESULTS: After statistical modelling that controlled for the effects of age, depression and apolipoprotein E genotype, HDL-C was significantly associated with better verbal learning and memory performance, specifically short and long delay-free recalls (F = 3.062; p < .05 and F = 3.2670; p < .05, respectively). CONCLUSION: Our cross-sectional findings suggest that the positive effect of HDL-C on verbal memory may be present much earlier than previously reported and provide further support for the role of HDL-C in healthy brain ageing. Further exploration of the protective effect of HDL-C on cognitive function in ageing is warranted through follow-up, longitudinal studies.
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Envejecimiento/sangre , Cognición/fisiología , Envejecimiento Cognitivo , Lipoproteínas HDL/sangre , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/genética , Apolipoproteínas E/genética , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Memoria/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Análisis de Regresión , Aprendizaje VerbalRESUMEN
The early diagnosis of Alzheimer's disease (AD) has become important to the reversal and treatment of neurodegeneration, which may be relevant to premature brain aging that is associated with chronic disease progression. Clinical proteomics allows the detection of various proteins in fluids such as the urine, plasma, and cerebrospinal fluid for the diagnosis of AD. Interest in lipidomics has accelerated with plasma testing for various lipid biomarkers that may with clinical proteomics provide a more reproducible diagnosis for early brain aging that is connected to other chronic diseases. The combination of proteomics with lipidomics may decrease the biological variability between studies and provide reproducible results that detect a community's susceptibility to AD. The diagnosis of chronic disease associated with AD that now involves genomics may provide increased sensitivity to avoid inadvertent errors related to plasma versus cerebrospinal fluid testing by proteomics and lipidomics that identify new disease biomarkers in body fluids, cells, and tissues. The diagnosis of AD by various plasma biomarkers with clinical proteomics may now require the involvement of lipidomics and genomics to provide interpretation of proteomic results from various laboratories around the world.
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Chronic neurodegenerative diseases are now associated with obesity and diabetes and linked to the developing and developed world. Interests in healthy diets have escalated that may prevent neurodegenerative diseases such as Parkinson's and Alzheimer's disease. The global metabolic syndrome involves lipoprotein abnormalities and insulin resistance and is the major disorder for induction of neurological disease. The effects of bacterial lipopolysaccharides (LPS) on dyslipidemia and NAFLD indicate that the clearance and metabolism of fungal mycotoxins are linked to hypercholesterolemia and amyloid beta oligomers. LPS and mycotoxins are associated with membrane lipid disturbances with effects on cholesterol interacting proteins, lipoprotein metabolism, and membrane apo E/amyloid beta interactions relevant to hypercholesterolemia with close connections to neurological diseases. The influence of diet on mycotoxin metabolism has accelerated with the close association between mycotoxin contamination from agricultural products such as apple juice, grains, alcohol, and coffee. Cholesterol efflux in lipoproteins and membrane cholesterol are determined by LPS with involvement of mycotoxin on amyloid beta metabolism. Nutritional interventions such as diets low in fat/carbohydrate/cholesterol have become of interest with relevance to low absorption of lipophilic LPS and mycotoxin into lipoproteins with rapid metabolism of mycotoxin to the liver with the prevention of neurodegeneration.
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Lipopolisacáridos/farmacología , Micotoxinas/toxicidad , Enfermedades Neurodegenerativas/etiología , Hipernutrición/complicaciones , Péptidos beta-Amiloides/metabolismo , Animales , Encéfalo/inmunología , Encéfalo/patología , Colesterol/metabolismo , Dislipidemias/complicaciones , Humanos , Metabolismo de los Lípidos , Enfermedades Neurodegenerativas/inmunologíaRESUMEN
Purpose: The objective of this paper was to compare the symptoms of asthenopia in patients at different levels of hyperopia and corrected for different accommodative efforts. Methods: This study is an experimental design and quantitative approach. Sixty-nine hyperopic patients aged between 15 and 40 were selected. Individuals with a diagnosis of accommodative insufficiency and paralysis, accommodative spasm or any type of ocular deviation were excluded. Subjects were randomly divided into four groups. Each one performed a nearvision task with different corrective lenses, varying the value of the accommodative effort. Results: There is significant reduction in the asthenopia score during the near-vision task when leaving 35% or more of the amplitude of accommodation in reserve. The linear regression showed that the variables total hyperopia (r = 0.109) and the difference between static and dynamic refraction (r = 0.135) did not obtain significant linear relationship to the asthenopia score. Conclusions: There is significant reduction in the asthenopia score when leaving 35% or more of the amplitude of accommodation in reserve. The symptoms of asthenopia are not associated to the severity of the hyperopic refractive error. The search for symptoms before the near vision task, using a questionnaire, related to the symptoms during the accommodative effort task, revealing the importance of searching for complaints about asthenopia during anamnesis, which can help ophthalmologists with prescriptions of glasses for hyperopic patients with asthenopia.
Objetivos: O presente estudo objetivou avaliar os efeitos do esforço acomodativo e do poder do erro refrativo nos sintomas de astenopia. Métodos: Trata-se de um modelo de estudo experimental e abordagem quantitativa, cuja amostra consistiu de 69 pacientes hipermetropes entre 15 e 40 anos de idade. Foram excluídos os indivíduos com diagnóstico de insuficiência ou paralisia da acomodação, espasmo de acomodação ou qualquer tipo de desvio ocular. Os pacientes foram alocados aleatoriamente em quatro grupos. Cada grupo realizou o trabalho de visão para perto com correções diferentes, variando o valor do esforço acomodativo. Resultado: Houve melhora significativa dos sintomas de astenopia com correções que proporcionaram mais de 35% da amplitude de acomodação em reserva. Não houve relação estatisticamente significativa entre os sintomas e o valor do erro refrativo. Conclusão: Há uma redução significativa dos sintomas quando os pacientes mantêm 35 % ou mais de sua acomodação em reserva. Os sintomas de astenopia não estão associados à gravidade do defeito hipermetrópico. A pesquisa de sintomas antes do teste, através de um questionário, foi o fator que melhor se relacionou com os sintomas durante o teste de visão para perto, revelando a importância da pesquisa das queixas de astenopia durante anamnese na prescrição de lentes para visão de perto.
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Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Acomodación Ocular , Astenopía , Anteojos , Hiperopía/diagnóstico , Errores de Refracción , Ensayo Clínico , Estudios de Evaluación como AsuntoRESUMEN
The pathological role of zinc in Alzheimer's disease (AD) is not yet fully elucidated, but there is strong evidence that zinc homeostasis is impaired in the AD brain and that this contributes to disease pathogenesis. In this study we examined the effects of zinc on the proteolysis of synthetic Apolipoprotein E (ApoE), a protein whose allelic variants differentially contribute to the onset/progression of disease. We have demonstrated that zinc promotes the proteolysis (using plasma kallikrein, thrombin and chymotrypsin) of synthetic ApoE in an isoform-specific way (E4>E2 and E3), resulting in more ApoE fragments, particularly for ApoE4. In the absence of exogenous proteases there was no effect of metal modulation on either lipidated or non-lipidated ApoE isoforms. Thus, increased zinc in the complex milieu of the ageing and AD brain could reduce the level of normal full-length ApoE and increase other forms that are involved in neurodegeneration. We further examined human plasma samples from people with different ApoE genotypes. Consistent with previous studies, plasma ApoE levels varied according to different genotypes, with ApoE2 carriers showing the highest total ApoE levels and ApoE4 carriers the lowest. The levels of plasma ApoE were not affected by either the addition of exogenous metals (copper, zinc or iron) or by chelation. Taken together, our study reveals that zinc may contribute to the pathogenesis of AD by affecting the proteolysis of ApoE, which to some extent explains why APOE4 carriers are more susceptible to AD.