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1.
Rev. cuba. med. mil ; 53(1)mar. 2024.
Article in Spanish | LILACS, CUMED | ID: biblio-1569888

ABSTRACT

Introducción: La enfermedad de Alzheimer, constituye un problema sanitario y social de gran magnitud; precisa de diagnóstico y terapéutica precoces. Se realizó una búsqueda de artículos sobre factores de riesgo y biomarcadores de la enfermedad en las bases de datos PubMed/Medline, Scopus, Scielo y Lilacs, y mediante el buscador Google académico; desde el año 2017 hasta el 2023, en idioma español, inglés y portugués. Objetivo: Analizar los factores de riesgo y los biomarcadores de la enfermedad de Alzheimer. Desarrollo: Los principales factores de riesgo encontrados son edad avanzada, menor educación, poca actividad física, hábito de fumar, consumo excesivo de alcohol, hipertensión arterial, diabetes, obesidad, depresión, pérdida o disminución de la audición, aislamiento social, los traumas craneales y la contaminación ambiental. Los biomarcadores fundamentales son: los marcadores que se utilizan en los estudios de neuroimágenes como la PET Amiloide, PET tau, PET FDG; y en LCR y plasma: Aß42, Aß42/Aß40, p tau 217, p tau 181, GFAP, y neurofilamentos de cadena ligeras. Conclusiones: Se requieren estudios longitudinales, a partir de la presencia de los factores de riesgo asociados a biomarcador, desde edades pregeriátricas en pacientes sanos, que tengan como salidas el deterioro cognitivo y el desarrollo de la demencia, para construir un modelo de predicción(AU)


Introduction: Alzheimer's disease is a health and social problem of great magnitude; it requires early diagnosis and therapy. A search for articles on risk factors and biomarkers of the disease was conducted; in the databases PubMed/Medline, Scopus, Scielo and Lilacs, and through the Google scholar search engine; from 2017 to 2023, in Spanish, English and Portuguese. Objective: To analyze the risk factors and biomarkers of Alzheimer's disease. Development: The main risk factors found are advanced age, lower education, little physical activity, smoking, excessive alcohol consumption, high blood pressure, diabetes, obesity, depression, hearing loss or decrease, social isolation, head trauma and environmental pollution. The fundamental biomarkers are: markers used in neuroimaging studies such as amyloid PET, tau PET, FDG PET; and in CSF and plasma: Aß42, Aß42/Aß40, p tau 217, p tau 181, GFAP, and light chain neurofilaments. Conclusions: Longitudinal studies are required, based on the presence of risk factors associated with biomarkers, from pregeriatric ages in healthy patients, which have cognitive impairment and the development of dementia as outputs, to build a prediction model(AU)


Subject(s)
Humans , Biomarkers , Risk Factors , Alzheimer Disease , Forecasting/methods , Amyloid , Social Isolation , Smoking , Longitudinal Studies , Positron-Emission Tomography/methods , Depression , Diabetes Mellitus , Environmental Pollution , Sedentary Behavior , Neuroimaging/methods , Cognitive Dysfunction , Binge Drinking , Hearing Loss , Hypertension , Obesity
2.
In. Anon. Instituto de Investigaciones de Ciencias Biológicas: publicaciones. Montevideo, IIBCE, impresión 2023. p.76-79, ilus.
Monography in Spanish | LILACS, UY-BNMED, BNUY | ID: biblio-1570983
3.
J. Oral Diagn ; 07: e20220003, 01/01/2022. ilus, tab
Article in English | LILACS, BBO | ID: biblio-1577193

ABSTRACT

Introduction: Amyloidosis is a condition related to aggregates of proteins in several organs of the body and can be systemic or localized. Amyloidosis localized in the oral cavity is extremely rare, being the tongue the more prevalent region. Objective: The aim of this present study is to describe a case of localized amyloidosis on the tongue and surgically removed. Methods: Also, a review of English-language literature of oral loca-lized amyloidosis from 1946 to 2021 was performed. Results: A total of 52 cases of oral localized amyloidosis were found in the literature. The majority of the cases was observed in female patients (53,84%), with an average age of 55,4 years (range 9 to 90 years) and the tongue being the most common localization (49,12%). Conclusions: Amyloidosis is a rare condition with atypical sign and symptoms. The systemic involvement should be evaluated due to worse prognosis of this condition and the possibility of organs failures. There is no standard treatment for local amyloidosis, but surgical excision is indicated to reduce the functional prejudice and pain, in symptomatic cases. (AU)


Subject(s)
Humans , Female , Aged , Amyloidosis , Mouth Diseases , Diagnosis , Amyloid
4.
Iatreia ; 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
5.
Chin. med. j ; Chin. med. j;(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)
Humans , Alzheimer Disease/etiology , Amyloid , Amyloid beta-Peptides , Risk Factors , tau Proteins
6.
J. Appl. Cogn. Neurosci. (Barranquilla) ; 1(1): 87-91, Dec 8, 2020. tab, graf
Article in English | LILACS, COLNAL | ID: biblio-1577691

ABSTRACT

Introduction: The MoCa (Montreal Cognitive Assessment) Screening test has become relevant in recent years in the screening of patients with Mild Cognitive Impairment (MCI). It is important to seek and study simple and reliable tools in clinical practices that correlate with biological markers that have been used to predict conversion from MCI to AD. Objective: To analyze the MOCA and its cognitive sub-scores and the relationship with Amyloid pathophysiology in Alzheimer's Disease. Methodology: 32 patients with MCI were studied, they were separated according positive (n: 20) and negative (n: 12) underlying amyloid pathology. The patients performed a extensive cognitive assessment that included MoCa Test. Results: MoCa Total Scores showed significantly different results between groups (p <0.001) as well as the Memory Score (MoCa MIS), the Executive (MoCa EIS), the Attentional Score (MoCa AIS)) (p < 0.001) and the Orientation Score (MoCa OIS)) (p < 0.05) with worse per-formance of patients with amyloid pathophysiology. Score of MoCa a cut-off point of < 24 was established, since the diagnostic sensitivity at this point was 83% and the specificity 70%. Conclusions: The MoCa is a useful tool to differentiate biomarker status in MCI. Future studies should study this tool in the prodromal phases of the disease.


Introducción: El MoCa (Montreal Cognitive Assesment) ha cobrado relevancia en los últimos años en el cribaje de pacientes con Deterioro Cognitivo Leve (DCL). El uso de herramientas clinicas simples y confiables con alta capacidad de pre-dicción de la conversion del DCL a Enfermedad de Alzheimer (EA) es de gran importancia. Objetivo: Analizar la capacidad del MoCa y sus subscores cognitivos para la detección de fisiopatología amiloide en un grupo de pacientes con DCL. Metodología: Se estudiaron 32 pacientes con DCL, se los separó según fisiopatología amiloide subyacente positiva (n:20) y negativa (n:12). Los pacientes realiza-ron una extensa evaluación cognitiva que incluyó en MoCA. Resultados: El Score Total del MoCa arrojó resultados significativamente diferentes entre grupos (p < 0.001) así como el Score de Memoria (MoCa MIS), el Ejecutivo (MoCa EIS), el Score Atencional (MoCa AIS) ) (p < 0.001) y el de Orientación (MoCa OIS) ) (p < 0.05) obteniendo un peor desempeño los pacientes con fisiopatología amiloide. Se establecio un punto de corte de < 24 para el Score Total del MoCa, ya que la sensibilidad en este punto fue de 83% y la especificidad de 70%. Conclusiones: El MoCa es una herramienta útil para utilizar en pacientes con Deterioro Cognitivo Leve debido a Enfermedad de Alzheimer. Futuros estudios deberían estudiar esta herramienta en las fases prodrómicas de la enfermedad.


Subject(s)
Humans , Cognitive Dysfunction , Amyloid
7.
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
8.
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)
Animals , Mice , Alzheimer Disease , Amyloid , Blood Platelets , Blotting, Western , Brain , Cognition Disorders , Dementia , Dendritic Spines , Enzyme-Linked Immunosorbent Assay , Excitatory Postsynaptic Potentials , Learning , Memory , Metabolism , Mice, Transgenic , Neurodegenerative Diseases , Neurons , Neuroprotective Agents , Plant Extracts , Plants , Plaque, Amyloid , Spatial Learning
9.
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
10.
Rev. bras. pesqui. méd. biol ; 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
11.
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
12.
Pesqui. vet. bras ; Pesqui. Vet. Bras. (Online);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
13.
Electron. j. biotechnol ; 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
14.
Article in English | WPRIM | ID: wpr-739212

ABSTRACT

BACKGROUND AND PURPOSE: Subjective cognitive decline (SCD) may be the first symptomatic stage of Alzheimer's disease (AD). Hence, a screening tool to characterize the patients' complaints and assess the risk of AD is required. We investigated the SCD neuroimaging biomarker distributions and the relevance between the self-report questionnaire and Alzheimer's pathologic changes. METHODS: Individuals aged 50 and above with consistent cognitive complaints without any objective cognitive impairments were eligible for the study. The newly developed questionnaire consisted of 2 parts; 10 questions translated from the ‘SCD-plus criteria’ and a Korean version of the cognitive failure questionnaire by Broadbent. All the subjects underwent physical examinations such as blood work, detailed neuropsychological tests, the self-report questionnaire, brain magnetic resonance imagings, and florbetaben positron emission tomography (PET) scans. Amyloid PET findings were interpreted using both visual rating and quantitative analysis. Group comparisons and association analysis were performed using SPSS (version 18.0). RESULTS: A total of 31 participants with SCD completed the study and 25.8% showed positive amyloid depositions. The degree of periventricular white matter hyperintensities (WMH) and hippocampal atrophy were more severe in amyloid-positive SCDs compared to the amyloid-negative group. In the self-reported questionnaire, the ‘informant's report a decline’ and ‘symptom's onset after 65 years of age’ were associated with more Alzheimer's pathologic changes. CONCLUSIONS: Amyloid-positive SCDs differed from amyloid-negative SCDs on WMH, hippocampal atrophy, and a few self-reported clinical features, which gave clues on the prediction of AD pathology.


Subject(s)
Alzheimer Disease , Amyloid , Atrophy , Biomarkers , Brain , Cognition Disorders , Mass Screening , Neuroimaging , Neuropsychological Tests , Pathology , Physical Examination , Plaque, Amyloid , Positron-Emission Tomography , White Matter
15.
Article in Korean | WPRIM | ID: wpr-787411

ABSTRACT

OBJECTIVES: Most studies of hippocampal metabolism(HM) in amnestic mild cognitive impairment(aMCI) gave inconsistent results. Our objective was to evaluate the effect of amyloid-beta(Aβ) status on hippocampal metabolism in aMCI.METHODS: Overall, 23 aMCI underwent three-dimensional magnetic resonance imaging(MRI), ¹⁸F-fluorodeoxyglucose-positron emission tomography(¹⁸FDG-PET) and ¹⁸F-Fluorbetaben amyloid positron emission tomography (amyloid-PET). According to Aβ status on amyloid PET, 23 aMCI were classified as either Aβ+aMCI(N=13) or Aβ−aMCI(N=10). The primary outcome was HM using ¹⁸FDG-PET and we investigate the difference on HM between Aβ+aMCI and Aβ−aMCI using analysis of variance(ANOVA) model, after controlling hippocampal volume.RESULTS: We found that HM was more decreased in Aβ+aMCI than Aβ−aMCI. This result was not changed after controlling hippocampal volume.CONCLUSION: Our findings suggest that Aβ+ is associated with decreased HM, regardless of hippocampal volume, in aMCI.


Subject(s)
Amyloid , Cognition Disorders , Metabolism , Pilot Projects , Plaque, Amyloid , Positron-Emission Tomography
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)
Humans , Amyloid , Brain Injuries , Brain , Dementia , Diabetes Mellitus , Insulin , Models, Animal , Obesity , Plaque, Amyloid , Presenilin-1 , Rodentia
17.
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)
Humans , Alzheimer Disease , Amyloid , Biomarkers , Brain , Chromatography, Liquid , Hydrocortisone , Metabolism , Metabolome , Metabolomics , Models, Statistical , Neurosciences
18.
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)
Humans , Alzheimer Disease , Amyloid , Brain , Carisoprodol , Immunohistochemistry , Mitochondrial Dynamics , Neurites , Neurodegenerative Diseases , Neurons , Pathology , Plaque, Amyloid , Pluripotent Stem Cells
19.
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)
Humans , Alzheimer Disease , Amyloid , Biomarkers , Brain , Cerebrospinal Fluid , Enzyme-Linked Immunosorbent Assay , Extracellular Fluid , Hydrocephalus , Metabolism , Positron-Emission Tomography
20.
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)
Humans , Alzheimer Disease , Amyloid , Blood Vessels , Cerebrovascular Disorders , Dementia , Diabetes Complications , Diabetes Mellitus, Type 2 , Islet Amyloid Polypeptide , Models, Animal , Neurologic Manifestations , Pathology , Prediabetic State , Rodentia
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