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1.
Iatreia ; 34(1): 64-70, ene.-mar. 2021. graf
Article in Spanish | LILACS | ID: biblio-1154359

ABSTRACT

RESUMEN La amiloidosis AL (antes denominada amiloidosis primaria) es una entidad sistémica poco frecuente, con incidencia desconocida en el mundo, que puede llegar a presentar compromiso cardíaco en casi la mitad de los pacientes, llevando a una cardiomiopatía restrictiva por depósito de tejido amiloide. A continuación, presentamos 3 casos de pacientes que consultaron por falla cardíaca aguda y síncope, en quienes finalmente se confirmó el diagnóstico de amiloidosis AL. Al final, se realiza una breve revisión de la literatura, enfatizando en los elementos clínicos para un diagnóstico temprano.


SUMMARY AL amyloidosis (formerly called primary amyloidosis) is a rare systemic entity, with an unknown incidence in the world, which can develop heart involvement in almost half of patients, leading to restrictive cardiomyopathy by amyloid tissue deposit. We present 3 cases of patients who consulted for acute heart failure and syncope, in which the diagnosis of AL amyloidosis was finally confirmed. We conclude with a brief review of the literature, emphasizing clinical elements for an early diagnosis.


Subject(s)
Humans , Aged , Syncope , Heart Failure , Amyloid , Cardiomyopathy, Restrictive , Heart
2.
Chinese Medical Journal ; (24): 2150-2159, 2021.
Article in English | WPRIM | ID: wpr-921114

ABSTRACT

Alzheimer disease (AD) is the most common type of dementia characterized by the progressive cognitive and social decline. Clinical drug targets have heavily focused on the amyloid hypothesis, with amyloid beta (Aβ), and tau proteins as key pathophysiologic markers of AD. However, no effective treatment has been developed so far, which prompts researchers to focus on other aspects of AD beyond Aβ, and tau proteins. Additionally, there is a mounting epidemiologic evidence that various environmental factors influence the development of dementia and that dementia etiology is likely heterogenous. In the past decades, new risk factors or potential etiologies have been widely studied. Here, we review several novel epidemiologic and clinical research developments that focus on sleep, hypoxia, diet, gut microbiota, and hearing impairment and their links to AD published in recent years. At the frontiers of AD research, these findings and updates could be worthy of further attention.


Subject(s)
Alzheimer Disease/etiology , Amyloid , Amyloid beta-Peptides , Humans , Risk Factors , tau Proteins
3.
Arq. bras. med. vet. zootec. (Online) ; 72(6): 2077-2085, Nov.-Dec. 2020. tab, graf
Article in Portuguese | LILACS, VETINDEX | ID: biblio-1142314

ABSTRACT

Este estudo teve como objetivo avaliar biomarcadores de mastite após terapia da secagem com plasma rico em plaquetas (PRP), associado ou não a antibiótico. Trinta e seis quartos mamários foram utilizados em três tratamentos (T): T1 - antibiótico (ATB), T2 - PRP e T3 - PRP + ATB. Amostras de leite foram coletadas antes da secagem (A1), no parto (D0) e 14, 30 e 60 dias pós-parto (D14, D30 e D60), para determinar contagem de células somáticas (CCS) e amiloide A (AA). O delineamento foi inteiramente ao acaso, com arranjo em parcelas subdivididas (SigmaPlot®). Dados de CCS foram transformados (log 10). As médias foram comparadas utilizando-se testes de Tukey ou Holm-Sidak (P<0,05). A CCS em A1 foi elevada em todos os grupos (P>0,05). No D30, CCS foi maior em T2 (P<0,05), igualando-se no D60. Não houve diferença na AA entre Ts em qualquer dia de coleta (P>0,05). Houve diferença nos momentos de coleta (P<0,05), A1 maior que D14 e D30. Houve uma correlação positiva fraca com CCS (0,280). Os tratamentos foram semelhantes em manter a saúde da glândula mamária na lactação subsequente. O PRP intramamário pode ser usado para terapia de vaca seca em casos de mastite subclínica.(AU)


This study aimed to evaluate biomarkers of mastitis after autologous platelet rich plasma (PRP) dry cow therapy, associated or not with antibiotic, compared to conventional treatment. Thirty-six mammary quarters were used in three treatments (T): T1 - antibiotic, T2 - PRP and T3 - PRP + ATB. Milk samples were collected before drying (A1), on calving (D0) and at 14, 30 and 60 days postpartum (D14, D30 and D60), for Somatic Cell Count (CCS) and amyloid dosage A (AA). The design was completely randomized with arrangement in subdivided plots (SigmaPlot ®). Data from CCS were transformed in log10. Means were compared using the Tukey or Holm-Sidak tests, at a 95% confidence level (P<0.05). CCS in A1 was elevated in allgroups (P>0.05). On D30 CCS was higher in T2 (P<0.05), matching D60. There was no difference in AA among T on any day of collection (P>0.05). There was difference in collection moments (P<0.05), A1 different from D14 and D30. There was a weak positive correlation with CCS (0.280). Three treatments were similar in maintaining the health of the mammary gland at subsequent lactation. PRP intramammary can be used for dry cow therapy in subclinical mastitis.(AU)


Subject(s)
Animals , Female , Cattle , Milk/chemistry , Platelet-Rich Plasma , Amyloid/analysis , Mastitis, Bovine/diagnosis , Biomarkers
6.
Korean Circulation Journal ; : 236-247, 2020.
Article in English | WPRIM | ID: wpr-811355

ABSTRACT

BACKGROUND AND OBJECTIVES: Recent studies have examined the structure-function relationship of high-density lipoprotein (HDL). This study aimed to identify and rank HDL-associated proteins involved in several biological function of HDL.METHODS: HDLs isolated from 48 participants were analyzed. Cholesterol efflux capacity, effect of HDL on nitric oxide production, and vascular cell adhesion molecule-1 expression were assessed. The relative abundance of identified proteins in the highest vs. lowest quartile was expressed using the normalized spectral abundance factor ratio.RESULTS: After adjustment by multiple testing, six proteins, thyroxine-binding globulin, alpha-1B-glycoprotein, plasma serine protease inhibitor, vitronectin, angiotensinogen, and serum amyloid A-4, were more abundant (relative abundance ratio ≥2) in HDLs with the highest cholesterol efflux capacity. In contrast, three proteins, complement C4-A, alpha-2-macroglobulin, and immunoglobulin mu chain C region, were less abundant (relative abundance ratio <0.5). In terms of nitric oxide production and vascular cell adhesion molecule-1 expression, no proteins showed abundance ratios ≥2 or <0.5 after adjustment. Proteins correlated with the functional parameters of HDL belonged to diverse biological categories.CONCLUSIONS: In summary, this study ranked proteins showing higher or lower abundance in HDLs with high functional capacities and newly identified multiple proteins linked to cholesterol efflux capacity.


Subject(s)
Amyloid , Angiotensinogen , Atherosclerosis , Cardiovascular Diseases , Cholesterol , Complement System Proteins , Immunoglobulin mu-Chains , Lipoproteins , Nitric Oxide , Plasma , Proteomics , Serine Proteases , Thyroxine-Binding Globulin , Vascular Cell Adhesion Molecule-1 , Vitronectin
7.
Article in English | WPRIM | ID: wpr-787140

ABSTRACT

Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia worldwide, and is mainly characterized by aggregated β-amyloid (Aβ). Increasing evidence has shown that plant extracts have the potential to delay AD development. The plant sterol β-Sitosterol has a potential role in inhibiting the production of platelet Aβ, suggesting that it may be useful for AD prevention. In the present study, we aimed to investigate the effect and mechanism of β-Sitosterol on deficits in learning and memory in amyloid protein precursor/presenilin 1 (APP/PS1) double transgenic mice. APP/PS1 mice were treated with β-Sitosterol for four weeks, from the age of seven months. Brain Aβ metabolism was evaluated using ELISA and Western blotting. We found that β-Sitosterol treatment can improve spatial learning and recognition memory ability, and reduce plaque load in APP/PS1 mice. β-Sitosterol treatment helped reverse dendritic spine loss in APP/PS1 mice and reversed the decreased hippocampal neuron miniature excitatory postsynaptic current frequency. Our research helps to explain and support the neuroprotective effect of β-Sitosterol, which may offer a novel pharmaceutical agent for the treatment of AD. Taken together, these findings suggest that β-Sitosterol ameliorates memory and learning impairment in APP/PS1 mice and possibly decreases Aβ deposition.


Subject(s)
Alzheimer Disease , Amyloid , Animals , Blood Platelets , Blotting, Western , Brain , Cognition Disorders , Dementia , Dendritic Spines , Enzyme-Linked Immunosorbent Assay , Excitatory Postsynaptic Potentials , Learning , Memory , Metabolism , Mice , Mice, Transgenic , Neurodegenerative Diseases , Neurons , Neuroprotective Agents , Plant Extracts , Plants , Plaque, Amyloid , Spatial Learning
8.
Braz. j. med. biol. res ; 53(6): e8625, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132515

ABSTRACT

Amyloidosis comprises a group of disorders that accumulate modified autologous proteins in organs, mainly the kidneys. Few studies have addressed the amyloid compartmental distribution and associated clinical outcomes. The aim of this study was to present a case series of renal amyloidosis correlating histopathological data with glomerular filtration rate (GFR) during kidney biopsy. We studied 53 cases reviewed by nephropathologists from 2000 to 2018 in a single kidney biopsy center in Brazil. GFR was estimated using the CKD-EPI formula. Cases were divided into Group A ≥60 and Group B <60 mL·min−1·(1.73 m2)−1 using the estimated GFR during kidney biopsy. Semiquantitative histopathological study was performed, including extension and distribution of amyloid deposits by compartments (glomeruli, tubulointerstitial tissue, and vessels). Statistical analyses were made to understand associations with lower GFR. No difference was seen for age, gender, proteinuria, hematuria, subtype of amyloid protein, arteriosclerosis, interstitial fibrosis/infiltrate, or glomerular and interstitial amyloid deposits. After a previous P value <0.1 in the descriptive analysis, the following variables were selected: globally sclerotic glomeruli, high blood pressure, and the extension of vascular amyloid deposition. A binary logistic regression model with GFR as the dependent variable showed history of hypertension and vascular amyloid to be robust and independent predictors of Group B <60 mL·min−1·(1.73 m2)−1. Beyond the histopathologic diagnosis of amyloidosis, a semiquantitative approach on renal biopsy could provide new insights. Vascular amyloid is an independent predictor of renal dysfunction in cases of renal amyloidosis.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Glomerular Filtration Rate , Amyloid/physiology , Amyloidosis/pathology , Kidney/pathology , Kidney Diseases/pathology , Biopsy , Retrospective Studies , Amyloidosis/physiopathology , Kidney/physiopathology , Kidney Diseases/physiopathology
9.
Bol. latinoam. Caribe plantas med. aromát ; 18(6): 544-554, nov. 2019. tab, ilus
Article in English | LILACS | ID: biblio-1102238

ABSTRACT

In this work, the inhibitory activity of a wide range of polysaccharide extracts from two Iranian and French strains of Agaricus subrufescens were evaluated toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, two extracts S9 and S'7 obtained from Iranian and French strains under different extraction conditions showed selective AChE inhibitory activity with IC50 values of 154.63 and 145.43 µg/mL, respectively. It should be noted that all extracts from both strains demonstrated no BChE inhibitory activity. S9 and S'7 were also tested for their effect on amyloid beta (Aß) aggregation, antioxidant activity, and neuroprotectivity. Their activity against Aß aggregation was comparable to that of donepezil as the reference drug but they induced moderate antioxidant activity by DPPH radical scavenging activity and negligible neuroprotectivity against Aß-induced damage.


En este trabajo, se evaluó la actividad inhibitoria de acetilcolinesterasa (AChE) y butirilcolinesterasa (BChE) para varios extractos de polisacáridos de dos cepas iraníes y francesas de Agaricus subrufescens. Los extractos más potentes mostraron valores de IC50 de 154,63 y 145 µg/ml para las cepas iraní (S9) y francesa (S'7), respectivamente, las cuales se obtuvieron de diferentes condiciones de extracción; sin embargo, todos los extractos no mostraron actividad inhibitoria de BChE. Además, S9 y S'7 se probaron para determinar su efecto sobre la agregación de beta-amiloide (Aß), así como su actividad antioxidante y neuroprotectora. Su actividad inhibitoria de la agregación de Aß fue comparable con donepezil, fármaco de referencia, pero indujeron una actividad antioxidante moderada, medida mediante la captación de radicales DPPH, y una neuroprotectora insignificante contra el daño inducido por Aß.


Subject(s)
Agaricus/chemistry , Alzheimer Disease/drug therapy , Amyloid/drug effects , Antioxidants/pharmacology , Picrates , Biphenyl Compounds , Butyrylcholinesterase , Cholinesterase Inhibitors/pharmacology , Neuroprotective Agents , Alzheimer Disease/enzymology , Fungal Polysaccharides/pharmacology
10.
Pesqui. vet. bras ; 39(8): 668-671, Aug. 2019. tab
Article in English | LILACS, VETINDEX | ID: biblio-1040732

ABSTRACT

The aim of this study was to evaluate the serum amyloid A (SAA) and biomarkers of muscle activity of horses submitted to show jumping activity. To do this, the variables SAA, glucose, lactate and the biomarkers creatine kinase (CK) and aspartate amino transferase (AST) were evaluated in 10 horses submitted to the show jumping exercise in a tournament for beginners. The evaluations occurred before exercise (T0), immediately after (T1), 30 minutes (T2), 60 minutes (T3) and 24 hours after the end (T4). Data were evaluated using analysis of variance for repeated measures. The statistical software SAEG 9.1 was used to verify the level of significance between the moments for P<0.05. Glucose presented a difference between the moments T0 (97.7±13.3mg/dL) and T1 (79.7±14.1mg/dL). Lactate presented elevation in T1 (15.3±6.1mmol/L) compared to the others T0 (3.8±0.8mmol/L), T2 (6.5±3.9mmol/L), T3 (5.3±2.2mmol/L) and T4 (5.1±1.6mmol/L). The CK showed a significant difference between T0 (82.8±51.2U/L) and T1 (140.1±58.5U/L) and between T4 (74.4±43.1U/L) with T1 (140.1±58.5U/L). The AST presented no difference between moments. The show jumping activity with one-meter obstacles did not induce changes in the SAA protein between the moments.(AU)


O objetivo deste estudo foi avaliar a amilóide sérica A (SAA) e biomarcadores de atividade muscular de equinos submetidos a atividade de salto, ou hipismo clássico. Para tanto, foram avaliadas as variáveis SAA, glicose, lactato e os biomarcadores creatina quinase (CK) e aspartatoaminotransferase (AST) em 10 equinos submetidos ao exercício de saltos em torneio para iniciantes. As avaliações ocorreram antes do exercício (T0), imediatamente após (T1), 30 minutos (T2), 60 minutos (T3) e 24 horas após o término (T4). Os dados foram avaliados utilizando análise de variância para medidas repetidas. O software estatístico SAEG 9.1 foi utilizado para verificar o nível de significância entre os momentos para P<0,05. A glicose diferenciou-se entre os momentos T0 (97.7±13.3mg/dL) e T1 (79.7±14.1mg/dL). O lactado apresentou elevação comparada com o momento T1(15.3±6.1mmol/L) e os demais T0 (3.8±0.8mmol/L), T2 (6.5±3.9mmol/L), T3 (5.3±2.2mmol/L) e T4 (5.1±1.6mmol/L). A CK mostrou diferença significativa entre T0 (82.8±51.2U/L) e T1 (140.1±58.5U/L) e entre T4 (74.4±43.1U/L) com T1 (140.1±58.5U/L). A AST não apresentou diferença entre os momentos. A atividade de hipismo clássico com obstáculos de um metro não induziu alterações na proteína SAA entre os momentos.(AU)


Subject(s)
Animals , Physical Conditioning, Animal/physiology , Biomarkers , Horses/physiology , Amyloid/blood , Motor Activity , Acute-Phase Proteins
11.
Electron. j. biotechnol ; 40: 1-9, July. 2019. tab, graf, ilus
Article in English | LILACS | ID: biblio-1053195

ABSTRACT

BACKGROUND: Microalgae are aquatic chlorophyll-containing organisms comprising unicellular microscopic forms, and their biomasses are potential sources of bioactive compounds, biofuels and food-based products. However, the neuroprotective effects of microalgal biomass have not been fully explored. In this study, biomass from two Chlorella species was characterized, and their antioxidant, anticholinesterase and anti-amyloidogenic activities were investigated. RESULTS: GC­MS analysis of the extracts revealed the presence of some phenols, sterols, steroids, fatty acids and terpenes. Ethanol extract of Chlorella sorokiniana (14.21 mg GAE/g) and dichloromethane extract of Chlorella minutissima (20.65 mg QE/g) had the highest total phenol and flavonoid contents, respectively. All the extracts scavenged 2,2-diphenyl-1-picrylhydrazyl, 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonate) and hydroxyl radicals. The highest metal chelating activity of the extracts was observed in the ethanol extracts of C. minutissima (102.60 µg/mL) and C. sorokiniana (107.84 µg/mL). Furthermore, the cholinesterase inhibitory activities of the extracts showed that ethanol extract of C. sorokiniana (13.34 µg/mL) exhibited the highest acetylcholinesterase inhibitory activity, while dichloromethane extract of C. minutissima (11.78 µg/mL) showed the highest butyrylcholinesterase inhibitory activity. Incubation of the ß-amyloid protein increased the aggregation of amyloid fibrils after 96 h. However, ethanol extract of C. sorokiniana and C. minutissima inhibited further aggregation of Aß1­42 and caused disaggregation of matured protein fibrils compared to the control. This study reveals the modulatory effects of C. sorokiniana and C. minutissima extracts on some mediators of Alzheimer's disease and provides insights into their potential benefits as functional food, nutraceutics or therapeutic agent for the management of this neurodegenerative disease.


Subject(s)
Chlorella/chemistry , Cholinesterase Inhibitors/pharmacology , Amyloid beta-Peptides/antagonists & inhibitors , Antioxidants/pharmacology , Phenols/analysis , Steroids/analysis , Sterols/analysis , Terpenes/analysis , Plant Extracts/pharmacology , Plant Extracts/chemistry , Cholinesterase Inhibitors/chemistry , Spectroscopy, Fourier Transform Infrared , Neuroprotective Agents , Biomass , Ethanol , Fatty Acids/analysis , Microalgae , Alzheimer Disease/prevention & control , Amyloid/drug effects , Gas Chromatography-Mass Spectrometry , Antioxidants/chemistry
12.
Article in English | WPRIM | ID: wpr-765671

ABSTRACT

Type 2 diabetes (T2D) increases the risk for cerebrovascular disease (CVD) and dementia. The underlying molecular mechanisms remain elusive, which hampers the development of treatment or/and effective prevention strategies. Recent studies suggest that dyshomeostasis of amylin, a satiety hormone that forms pancreatic amyloid in patients with T2D, promotes accumulation of amylin in cerebral small blood vessels and interaction with Alzheimer's disease (AD) pathology. Overexpression of human amylin in rodents (rodent amylin does not form amyloid) leads to late-life onset T2D and neurologic deficits. In this Review, we discuss clinical evidence of amylin pathology in CVD and AD and identify critical characteristics of animal models that could help to better understand molecular mechanisms underlying the increased risk of CVD and AD in patients with prediabetes or T2D.


Subject(s)
Alzheimer Disease , Amyloid , Blood Vessels , Cerebrovascular Disorders , Dementia , Diabetes Complications , Diabetes Mellitus, Type 2 , Humans , Islet Amyloid Polypeptide , Models, Animal , Neurologic Manifestations , Pathology , Prediabetic State , Rodentia
13.
Article in English | WPRIM | ID: wpr-764337

ABSTRACT

BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) could be misleading in idiopathic normal-pressure hydrocephalus (iNPH). We therefore investigated the CSF biomarkers in 18F-florbetaben amyloid-negative positron-emission tomography (PET) [amyloid PET(−)] iNPH, amyloid-positive PET [amyloid PET(+)] AD, and cognitively normal (CN) subjects. METHODS: Ten amyloid PET(+) AD patients (56.7±5.6 years old, mean±standard deviation), 10 amyloid PET(−) iNPH patients (72.8±4.5 years old), and 8 CN subjects (61.2±6.5 years old) were included. We measured the levels of β-amyloid (Aβ)40, Aβ42, total tau (t-tau) protein, and phosphorylated tau (p-tau) protein in the CSF using enzyme-linked immunosorbent assays. RESULTS: The level of Aβ42 and the Aβ42/Aβ40 ratio in the CSF were significantly lower in AD than in iNPH or CN subjects. The Aβ40 level did not differ significantly between AD and iNPH (p=1.000), but it did between AD and CN subjects (p=0.032). The levels of both t-tau and p-tau were higher in AD than in iNPH or CN subjects. The levels of Aβ42, Aβ40, t-tau, and p-tau were lower in iNPH than in CN subjects, but there was no significant difference after controlling for age. CONCLUSIONS: Our results suggest that the mechanism underlying low CSF Aβ levels differs between amyloid PET(−) iNPH and amyloid PET(+) AD subjects. The lower levels of all CSF biomarkers in iNPH patients might be due to reduced clearances from extracellular fluid and decreased brain metabolism of the periventricular zone in iNPH resulting from glymphatic dysfunction.


Subject(s)
Alzheimer Disease , Amyloid , Biomarkers , Brain , Cerebrospinal Fluid , Enzyme-Linked Immunosorbent Assay , Extracellular Fluid , Humans , Hydrocephalus , Metabolism , Positron-Emission Tomography
14.
Experimental Neurobiology ; : 329-336, 2019.
Article in English | WPRIM | ID: wpr-763771

ABSTRACT

Alzheimer's Disease (AD) is a progressive neurodegenerative disease, which is pathologically defined by the accumulation of amyloid plaques and hyper-phosphorylated tau aggregates in the brain. Mitochondrial dysfunction is also a prominent feature in AD, and the extracellular Aβ and phosphorylated tau result in the impaired mitochondrial dynamics. In this study, we generated an induced pluripotent stem cell (iPSC) line from an AD patient with amyloid precursor protein (APP) mutation (Val715Met; APP-V715M) for the first time. We demonstrated that both extracellular and intracellular levels of Aβ were dramatically increased in the APP-V715M iPSC-derived neurons. Furthermore, the APP-V715M iPSC-derived neurons exhibited high expression levels of phosphorylated tau (AT8), which was also detected in the soma and neurites by immunocytochemistry. We next investigated mitochondrial dynamics in the iPSC-derived neurons using Mito-tracker, which showed a significant decrease of anterograde and retrograde velocity in the APP-V715M iPSC-derived neurons. We also found that as the Aβ and tau pathology accumulates, fusion-related protein Mfn1 was decreased, whereas fission-related protein DRP1 was increased in the APP-V715M iPSC-derived neurons, compared with the control group. Taken together, we established the first iPSC line derived from an AD patient carrying APP-V715M mutation and showed that this iPSC-derived neurons exhibited typical AD pathological features, including a distinct mitochondrial dysfunction.


Subject(s)
Alzheimer Disease , Amyloid , Brain , Carisoprodol , Humans , Immunohistochemistry , Mitochondrial Dynamics , Neurites , Neurodegenerative Diseases , Neurons , Pathology , Plaque, Amyloid , Pluripotent Stem Cells
15.
Experimental Neurobiology ; : 376-389, 2019.
Article in English | WPRIM | ID: wpr-763767

ABSTRACT

Despite significant advances in neuroscience research over the past several decades, the exact cause of AD has not yet fully understood. The metabolic hypothesis as well as the amyloid and tau hypotheses have been proposed to be associated with AD pathogenesis. In order to identify metabolome signatures from the postmortem brains of sporadic AD patients and control subjects, we performed ultra performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometer (UPLC-LTQ–Orbitrap-MS). Not only our study identified new metabolome signatures but also verified previously known metabolome profiles in the brain. Statistical modeling of the analytical data and validation of the structural assignments discovered metabolic biomarkers associated with the AD pathogenesis. Interestingly, hypotaurin, myo-inositol and oxo-proline levels were markedly elevated in AD while lutamate and N-acetyl-aspartate were decreased in the postmortem brain tissue of AD patients. In addition, neurosteroid level such as cortisol was significantly increased in AD. Together, our data indicate that impaired amino acid metabolism is associated with AD pathogenesis and the altered amino acid signatures can be useful diagnostic biomarkers of AD. Thus, modulation of amino acid metabolism may be a possible therapeutic approach to treat AD.


Subject(s)
Alzheimer Disease , Amyloid , Biomarkers , Brain , Chromatography, Liquid , Humans , Hydrocortisone , Metabolism , Metabolome , Metabolomics , Models, Statistical , Neurosciences
16.
Article in English | WPRIM | ID: wpr-763690

ABSTRACT

The link of diabetes with co-occurring disorders in the brain involves complex and multifactorial pathways. Genetically engineered rodents that express familial Alzheimer's disease-associated mutant forms of amyloid precursor protein and presenilin 1 (PSEN1) genes provided invaluable insights into the mechanisms and consequences of amyloid deposition in the brain. Adding diabetes factors (obesity, insulin impairment) to these animal models to predict success in translation to clinic have proven useful at some extent only. Here, we focus on contributing factors to diabetic brain injury with the aim of identifying appropriate animal models that can be used to mechanistically dissect the pathophysiology of diabetes-associated cognitive dysfunction and how diabetes medications may influence the development and progression of cognitive decline in humans with diabetes.


Subject(s)
Amyloid , Brain Injuries , Brain , Dementia , Diabetes Mellitus , Humans , Insulin , Models, Animal , Obesity , Plaque, Amyloid , Presenilin-1 , Rodentia
17.
Yonsei Medical Journal ; : 640-650, 2019.
Article in English | WPRIM | ID: wpr-762096

ABSTRACT

PURPOSE: Alzheimer's disease (AD) is the most common neurodegenerative disease, with a rising prevalence worldwide. Long noncoding RNAs (lncRNAs) have been found to play important roles in the development and treatment of AD. However, the exact role of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in neuronal damage in AD is largely unknown. MATERIALS AND METHODS: The AD model was established in SH-SY5Y and SK-N-SH cells via treatment with amyloid β1−42 (Aβ). The expression of NEAT1 and microRNA-107 (miR-107) was measured by quantitative real-time polymerase chain reaction. Cell viability and apoptosis were detected by MTT assay, immunocytochemistry, and flow cytometry. The expression of phosphorylated tau protein (p-Tau) was measured by Western blot. The interaction between NEAT1 and miR-107 was explored by bioinformatics analysis, luciferase activity, and RNA immunoprecipitation assays. RESULTS: NEAT1 expression was enhanced in Aβ-treated SH-SY5Y and SK-N-SH cells, and its knockdown attenuated Aβ-induced inhibition of viability and promotion of apoptosis and p-Tau levels. NEAT1 was indicated as a decoy of miR-107. miR-107 abundance was reduced in Aβ-treated cells, and its overexpression reversed Aβ-induced injury. Moreover, interference of miR-107 abated silencing of NEAT1-mediated inhibition of neuronal damage in Aβ-treated SH-SY5Y and SK-N-SH cells. CONCLUSION: LncRNA NEAT1 aggravated Aβ-induced neuronal damage by sponging miR-107, indicating a novel avenue for treatment of AD.


Subject(s)
Alzheimer Disease , Amyloid , Apoptosis , Blotting, Western , Cell Survival , Computational Biology , Flow Cytometry , Immunohistochemistry , Immunoprecipitation , Luciferases , Neurodegenerative Diseases , Neurons , Prevalence , Real-Time Polymerase Chain Reaction , RNA , RNA, Long Noncoding , tau Proteins
18.
Yonsei Medical Journal ; : 935-943, 2019.
Article in English | WPRIM | ID: wpr-762039

ABSTRACT

PURPOSE: This study aimed to identify the neural basis of executive function (EF) in amnestic mild cognitive impairment (aMCI) according to beta-amyloid (Aβ) positivity. Furthermore, we explored if the identified brain areas could serve as predictors for clinical progression. MATERIALS AND METHODS: We included individuals with aMCI using data from [¹⁸F]-florbetapir-positron emission tomography (PET), fluorodeoxyglucose-PET, and EF scores, as well as follow-up clinical severity scores at 1 and 5 years from baseline from the Alzheimer's Disease Neuroimaging Initiative database. The correlations between EF score and regional cerebral glucose metabolism (rCMglc) were analyzed separately for aMCI with low Aβ burden (aMCI Aβ−, n=230) and aMCI with high Aβ burden (aMCI Aβ+, n=268). Multiple linear regression analysis was conducted to investigate the associations between rCMglc and clinical progression. RESULTS: Longitudinal courses differed between aMCI Aβ− and aMCI Aβ+ groups. On average, aMCI Aβ− subjects maintained their level of clinical severity, whereas aMCI Aβ+ subjects showed progression. EF impairment in aMCI Aβ− was related to the anterior cingulate cortex (ACC), whereas that in aMCI Aβ+ was related to Alzheimer's Disease-vulnerable brain regions. ACC and the posterior cingulate cortex were associated with clinical progression in aMCI Aβ− and aMCI Aβ+, respectively. CONCLUSION: Our findings suggest that although MCI subjects showed similar behavioral phenotypes at the time of diagnosis, EF and further progression were associated with different brain regions according to Aβ burden. Clarification of the etiologies and nature of EF impairment in aMCI are critical for disease prognosis and management.


Subject(s)
Alzheimer Disease , Amyloid , Brain , Cognition , Diagnosis , Executive Function , Follow-Up Studies , Glucose , Gyrus Cinguli , Linear Models , Metabolism , Cognitive Dysfunction , Neuroimaging , Phenotype , Positron-Emission Tomography , Prognosis
19.
Article in English | WPRIM | ID: wpr-786490

ABSTRACT

PURPOSE: To investigate regional cerebral amyloid beta retention in cognitively normal Korean adults using F-18 florbetaben (FBB).METHODS: We prospectively analyzed F-18 FBB positron emission tomography (PET)/CT scans of 30 cognitively healthy adults (age range, 50??0 years) using automated quantification. The standardized uptake value ratios (SUVRs) of F-18 FBB were calculated for predefined regions by normalizing the regional count with cerebellar cortex.RESULTS: The distribution of amyloid beta for each brain region revealed no age-related trends (p > 0.05). From all subjects, mean SUVR of amyloid deposit was 1.30 ± 0.18. The right parietal lobe showed the highest SUVR value (1.46 ± 0.23), whereas the right frontal lobe and left precuneus showed the lowest SUVR (1.23 ± 0.25).CONCLUSIONS: We provide reference values of normative data obtained from healthy elderly Koreans and suggest its use for accurate diagnosis of patients with Alzheimer's disease.


Subject(s)
Adult , Aged , Alzheimer Disease , Amyloid , Brain , Cerebellar Cortex , Diagnosis , Frontal Lobe , Humans , Parietal Lobe , Plaque, Amyloid , Positron-Emission Tomography , Prospective Studies , Reference Values
20.
Article in English | WPRIM | ID: wpr-786489

ABSTRACT

PURPOSE: Although quantification of amyloid positron emission tomography (PET) is important for evaluating patients with cognitive impairment, its routine clinical use is hampered by complicated preprocessing steps and required MRI. Here, we suggested a one-step quantification based on deep learning using native-space amyloid PET images of different radiotracers acquired from multiple centers.METHODS: Amyloid PET data of the Alzheimer Disease Neuroimaging Initiative (ADNI) were used for this study. A training/validation consists of 850 florbetapir PET images. Three hundred sixty-six florbetapir and 89 florbetaben PET images were used as test sets to evaluate the model. Native-space amyloid PET images were used as inputs, and the outputs were standardized uptake value ratios (SUVRs) calculated by the conventional MR-based method.RESULTS: The mean absolute errors (MAEs) of the composite SUVR were 0.040, 0.060, and 0.050 of training/validation and test sets for florbetapir PETand a test set for florbetaben PET, respectively. The agreement of amyloid positivity measured by Cohen's kappa for test sets of florbetapir and florbetaben PET were 0.87 and 0.89, respectively.CONCLUSION: We suggest a one-step quantification method for amyloid PET via a deep learning model. The model is highly reliable to quantify the amyloid PET regardless of multicenter images and various radiotracers.


Subject(s)
Alzheimer Disease , Amyloid , Cognition Disorders , Humans , Learning , Magnetic Resonance Imaging , Methods , Neuroimaging , Positron-Emission Tomography
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