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1.
Wien Klin Wochenschr ; 132(1-2): 42-46, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31832773

RESUMO

Previous studies have highlighted that spermidine has the ability to trigger the important process of dissolving amyloid-beta plaques by autophagy. This manuscript focuses on the correlation of serum spermidine levels between age and between performance in mini-mental state examinations. It will serve as a premise for an ongoing multicentric placebo-controlled study, which focuses on the effect of oral spermidine supplementation on memory performance. Memory tests were carried out on 80 subjects aged 60-96 years old in 6 nursing homes in Styria. Blood samples were taken for the determination of spermidine concentration. The results showed a significant correlation between the spermidine concentration and the mini-mental state examination score (p = 0.025). On the basis of the dependence demonstrated it can be concluded that spermidine might be suitable as a biomarker for the diagnosis of neurocognitive changes (senile dementia or Alzheimer's disease).


Assuntos
Doença de Alzheimer , Demência , Espermidina , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Demência/sangue , Demência/diagnóstico , Humanos , Memória , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Espermidina/sangue
2.
Clin Biochem ; 76: 24-30, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31786207

RESUMO

OBJECTIVE: The development of blood-based biomarkers for early diagnosis and treatment of Alzheimer's disease (AD) is desirable. In AD model mouse brain and neuronal cells, Abelson helper integration site-1 (AHI1) protein is reduced. AHI1 facilitates intracellular amyloid precursor protein (APP) translocation to inhibit amyloidogenic pathology of AD, and thus may be an AD biomarker. METHODS: This study was conducted among 32 AD patients and 54 healthy control (HC) subjects. AHI1-related protein levels from initially collected serum samples in each group were screened using Western blotting. The protein concentrations of AHI1 and amyloid-ß (Aß), peptide(s) derived from APP, from all serum samples were analyzed using ELISA. RESULTS: In AD serum, AHI1 and a large truncated C-terminal APP fragment were significantly reduced. The average concentrations of serum AHI1 and Aß in AD were significantly lower than those in HC. Notably, AHI1 concentration in HC serum was decreased in an age-dependent manner, while it was consistently low in AD serum and had no correlation with Aß or mini-mental state examination score. The receiver operating characteristic analysis on all subjects demonstrated an area under curve (AUC) value of 0.7 for AHI1 on AD diagnosis, while the AUC increased to 0.82 on the subjects younger than 77 years old, suggesting a good diagnostic performance of serum AHI1 for AD especially at relatively young age. CONCLUSION: An early event of AHI1 reduction in the body of AD patients was observed. Serum AHI1 may be valuable for early diagnosis of AD.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/sangue , Doença de Alzheimer/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Taiwan
3.
J Pharm Biomed Anal ; 177: 112874, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31542420

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease that seriously affects daily life. Schisandra chinensis (Turcz.) Baill. Fructus (SCF) and Alpinia oxyphylla Miq. Fructus (AOF) have been regarded as classical herbs for dementia since ancient times. Alpinia oxyphylla Miq.-Schisandra chinensis (Turcz.) Baill. herb pair (ASHP) is the compatible form of the two herbs. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for the simultaneous determination of protocatechuic acid, chrysin, schisandrin, gomisin A, gomisin B, nootkatone, deoxyschizandrin, schisandrin B and schisandrin C in rat plasma. The pharmacokinetic differences of the above nine active components in normal rats and AD model rats after oral administration of SCF, AOF, and ASHP ethanol extracts were investigated. Chloramphenicol and bifendate were used as the internal standards. Extraction of plasma sample was by liquid-liquid extraction with ethyl acetate. A SBC18 column (2.1 mm × 100 mm, 1.8 µm) was used in this experiment at a flow rate of 0.3 mL/min at 30 °C with linear gradient elution using acetonitrile and water containing 0.1% formic acid. This study showed ASHP can improve the absorption of protocatechuic acid, chrysin, schisandrin, gomisin B, nootkatone, deoxyschizandrin, schisandrin B and schisandrin C in vivo and slow down part of these components' elimination. In addition, compared with normal rats, the pharmacokinetic parameters changed significantly in AD model rats' plasma after oral administration of ASHP. Hence, these may be the pharmacokinetic mechanism of ASHP, in addition to serving as a potential agent in the treatment of AD.


Assuntos
Alpinia/química , Doença de Alzheimer/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Medicamentos de Ervas Chinesas/farmacocinética , Schisandra/química , Administração Oral , Doença de Alzheimer/sangue , Doença de Alzheimer/etiologia , Peptídeos beta-Amiloides/administração & dosagem , Peptídeos beta-Amiloides/toxicidade , Animais , Cromatografia Líquida de Alta Pressão/métodos , Modelos Animais de Doenças , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Humanos , Injeções Intraventriculares , Masculino , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/toxicidade , Ratos , Espectrometria de Massas em Tandem/métodos
4.
Medicina (B Aires) ; 79(Spec 6/1): 546-551, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31864224

RESUMO

Alzheimer disease (AD) is one of the major unresolved health burdens accompanying the increase in life expectancy. The great paradigm shift for this disease has resulted from finding amyloid deposition and neurobrillary degeneration 20 years and 10 years, respectively, prior to onset of the typical clinical memory loss symptoms. The advent of AD biomarkers has enabled a molecular definition of AD, making the clinical definition almost dispensable. Various types of AD biomarkers are available in our country. Each biomarker reflects a particular process and stage of the disease. Although costs restrict their use, the biomarker analysis may be justified in certain clinical scenarios, such as an early onset or an atypical presentation of the disease. Today, the usefulness of biomarkers in AD clinical research is beyond question. Furthermore, the introduction of biomarkers into medical practice has led to significant changes in therapeutic interventions, even in the absence of disease-modifying drugs.


Assuntos
Doença de Alzheimer/diagnóstico , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Humanos , Imagem por Ressonância Magnética , Neuroimagem/métodos , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X
5.
BMC Neurol ; 19(1): 284, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722673

RESUMO

BACKGROUND: We aimed to comprehensively explore the associations between serum 25(OH)D deficiency and risk of dementia and Alzheimer's disease(AD). METHODS: We systematically searched Pubmed, the Cochrane Library, Embase and the reference lists of pertinent review articles for relevant articles published from database inception up until January 2019. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with random effects models using the Stata 12.0 statistical software package. RESULTS: Twelve prospective cohort studies and four cross-sectional studies were included in this meta-analysis. The pooled HRs of dementia and AD, respectively, were 1.32 (95%CI: 1.16, 1.52) and 1.34 (95%CI: 1.13, 1.60) for vitamin D deficiency (< 20 ng/ml). In the subgroup analyses, the pooled HRs of dementia and AD, respectively, were 1.48 (95%CI: 1.19, 1.85) and 1.51 (95%CI: 1.04, 2.18) for moderate vitamin D deficiency (10-20 ng/ml) and 1.20 (95%CI: 0.99, 1.44) and 1.36 (95%CI: 1.01, 1.84) for severe vitamin D deficiency (< 10 ng/ml). CONCLUSION: There are significant associations between vitamin D deficiency and both dementia and AD. There are stronger associations between severe vitamin D deficiency (< 10 ng/ml) and both dementia and AD compared to moderate vitamin D deficiency (10-20 ng/ml).


Assuntos
Doença de Alzheimer/sangue , Demência/sangue , Deficiência de Vitamina D/complicações , Algoritmos , Estudos Transversais , Bases de Dados Factuais , Humanos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Vitamina D/sangue
6.
Medicine (Baltimore) ; 98(47): e17970, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764802

RESUMO

Alzheimer disease (AD) is the most common neurodegenerative disease in the world. The relationship between AD and homocysteine (Hcy) is contradictory.A community-based investigation was conducted to find patients with AD in a vitamin B deficient population (≥55 years old) in Lüliang area in China. Venous blood samples were collected. Serum Hcy, folate, and vitamin B12 were measured. For each case, 4 controls were selected matched with age to evaluate the relationship between Hcy and AD.The crude prevalence of AD among people ages 55 years or older in this area was 8.60%. There were significant differences in serum Hcy and B12 between the case and control groups. We found that the higher level of serum Hcy was associated with a high risk of AD, and higher education level, higher folate and B12 concentration were protective factors to AD.Adjustment of diet structure and supplementation of folate and B12 may offer potential therapeutic measures in this area.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/etiologia , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/complicações , Ácido Fólico/sangue , Homocisteína/sangue , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/complicações , Vitamina B 12/sangue , Idoso , Idoso de 80 Anos ou mais , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
Neurology ; 93(22): e2053-e2064, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31645469

RESUMO

OBJECTIVE: The associations between trans fatty acids and dementia have been unclear. We investigated the prospective association between serum elaidic acid (trans 18:1 n-9) levels, as an objective biomarker for industrial trans fat, and incident dementia and its subtypes. METHODS: In total, 1,628 Japanese community residents aged 60 and older without dementia were followed prospectively from when they underwent a screening examination in 2002-2003 to November 2012 (median 10.3 years, interquartile range 7.2-10.4 years). Serum elaidic acid levels were measured using gas chromatography/mass spectrometry and divided into quartiles. The Cox proportional hazards model was used to estimate the hazard ratios for all-cause dementia, Alzheimer disease (AD), and vascular dementia by serum elaidic acid levels. RESULTS: During the follow-up, 377 participants developed some type of dementia (247 AD, 102 vascular dementia). Higher serum elaidic acid levels were significantly associated with greater risk of developing all-cause dementia (p for trend = 0.003) and AD (p for trend = 0.02) after adjustment for traditional risk factors. These associations remained significant after adjustment for dietary factors, including total energy intake and intakes of saturated and polyunsaturated fatty acids (both p for trend <0.05). No significant associations were found between serum elaidic acid levels and vascular dementia. CONCLUSIONS: The findings suggest that higher serum elaidic acid is a possible risk factor for the development of all-cause dementia and AD in later life. Public health policy to reduce industrially produced trans fatty acids may assist in the primary prevention of dementia.


Assuntos
Doença de Alzheimer/epidemiologia , Demência Vascular/epidemiologia , Ácidos Oleicos/sangue , Ácidos Graxos Trans/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Demência/sangue , Demência/epidemiologia , Demência Vascular/sangue , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais
8.
Folia Neuropathol ; 57(2): 106-116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556571

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative dementia in adults. Pathogenesis of AD depends on various factors, including APOE genetic variants, apolipoprotein E (apoE) phenotype and oxidative stress, which may promote both DNA and RNA damage, including non-coding RNA (ncRNA). Among ncRNAs, microRNA (miRNA) is known to contribute to pathologic processes in AD. The aim of the study was to analyse the plasma concentration of apoE by ELISA as well as the plasma levels of miR-107 and miR-650 by qPCR in relation to APOE genetic variants and clinical features including the age of onset and dementia severity in 64 AD patients and 132 controls. Our data showed that a low apoE plasma concentration was a risk factor for developing AD (OR = 5.18, p = 6.58E-06) and was particularly pronounced in severe dementia (p < 0.001) and correlated with cognitive functions (R = 0.295, p = 0.020), similarly as the level of miR-650 (R = 0.385, p = 0.033). The presence of APOE E4 allele in both AD patients and controls led to a reduction in apoE, while APOE E3/E3 genotype was associated with an increased apoE concentration and level of miR-107 in AD (p < 0.05) which was inversely correlated with the number of APOE E4 alleles (R = -0.448, p = 0.009). Additionally, patients with the onset at 60-69 years of age showed a reduced level of miR-107 (p < 0.05, as compared to AD above 80 years of age). Changed levels of plasma apoE, miR-107 and miR-650 may be a marker of the neurodegenerative process in the course of AD, associated with amyloid ß metabolism and inordinate cell cycle.


Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , MicroRNAs/sangue , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Apolipoproteínas E/sangue , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
10.
Clin Interv Aging ; 14: 1303-1317, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409980

RESUMO

Vitamin E has been proposed as a potential clinical intervention for Alzheimer's disease (AD) given the plausibility of its various biological functions in influencing the neurodegenerative processes associated with the condition. The tocopherol and tocotrienol isoforms of vitamin E have multiple properties including potent antioxidant and anti-inflammatory characteristics, in addition to influences on immune function, cellular signalling and lowering cholesterol. Several of these roles offer a theoretical rationale for providing benefit for the treatment of AD-associated pathology. Diminished circulating concentrations of vitamin E have been demonstrated in individuals with AD. Reduced plasma levels have furthermore been associated with an increased risk of AD development while intake, particularly from dietary sources, may limit or reduce the rate of disease progression. This benefit may be linked to synergistic actions between vitamin E isoforms and other micronutrients. Nevertheless, randomised trials have found limited and inconsistent evidence of vitamin E supplementation as an effective clinical intervention. Thus, despite a strong rationale in support of a beneficial role for vitamin E for the treatment of AD, the evidence remains inconclusive. Several factors may partly explain this discrepancy and represent the difficulties of translating complex laboratory evidence and dietary interactions into clinical interventions. Methodological design limitations of existing randomised trials and restrictions to supplementation with a single vitamin E isoform may also limit the influence of effect. Moreover, several factors influence individual responsiveness to vitamin E intake and recent findings suggest variation in the underlying genetic architecture attenuates vitamin E biological availability and activity which likely contributes to the variation in clinical responsiveness and the failure of randomised trials to date. Importantly, the clinical safety of vitamin E remains controversial and warrants further investigation.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/epidemiologia , Vitamina E/sangue , Colesterol/sangue , Dieta , Suplementos Nutricionais , Progressão da Doença , Humanos , Masculino , Estado Nutricional , Resultado do Tratamento
11.
Biosens Bioelectron ; 143: 111561, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31446202

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with severe memory loss and impaired cognitive skills. A common pathological change found in AD-affected brains is the accumulation of a peptide named amyloid-ß (Aß) that can form plaques. Aß aggregates are visible to structural scanning tools; however, these bulky and expensive instruments are accessible to trained personnel in clinical settings only, thus hampering timely diagnosis of the disease, particularly in low-resource settings. In this work, we design an organic electrochemical transistor (OECT) for in vitro detection of Aß aggregates in human serum. The OECT channel is integrated with a nanostructured isoporous membrane which has a strong affinity for Aß aggregates. The detection mechanism relies on the membrane capturing Aß aggregates larger than the size of its pores and thus blocking the penetration of electrolyte ions into the channel underneath. Combining the high transconductance of the OECT with the precise porosity and selectivity of the membrane, the device detects the presence of Aß aggregates in human serum samples with excellent sensitivity. This is the first-time demonstration of a biofunctionalized, nanostructured, and isoporous membrane integrated with a high-performance transistor for biosensing. This robust, low-power, non-invasive, and miniaturized sensor aids in the development of point-of-care tools for early diagnosis of AD.


Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/isolamento & purificação , Técnicas Biossensoriais , Doença de Alzheimer/sangue , Encéfalo/metabolismo , Encéfalo/patologia , Humanos , Membranas Artificiais , Nanoestruturas/química , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Transistores Eletrônicos
12.
Food Funct ; 10(9): 5656-5668, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31433414

RESUMO

Schisandra chinensis (Turcz.) Baill (S. chinensis), a functional food, is used as a tonic and sedative agent in traditional Chinese medicine. Modern pharmacological research has proved that S. chinensis could prevent and treat age-related neurodegenerative diseases. The presence of bioactive lignans in S. chinensis is the main reason for its neuroprotective and cognitive enhancement effects. This study aimed to clarify the mechanism of lignans in S. chinensis in ameliorating learning and memory deficits in Alzheimer's disease (AD) animals. The step-down test and Morris water maze (MWM) test were used to verify the effects of lignans in S. chinensis on learning and memory in AD animals. Then, metabolomics approaches based on ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) were used to clarify the mechanism of lignans in S. chinensis in treating AD. Finally, quantitative analysis of AD-related neurotransmitters in the brain was conducted after treatment with lignans in S. chinensis. In the MWM and step-down tests, lignans in S. chinensis showed a clear ability to ameliorate the impaired learning and memory of AD animals. A total of 31 endogenous metabolites were identified after treatment with lignans in S. chinensis, which were associated with lignans ameliorating learning and memory. These biomarkers were mainly associated with polyunsaturated fatty acid metabolism and amino acid and vitamin metabolism. Moreover, lignans in S. chinensis upregulated the levels of γ-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT), acetylcholine (Ach), norepinephrine (NE) and glycine (Gly) and downregulate the level of aspartic acid (Asp). Lignans in S. chinensis might alleviate the neurotoxic effects of neurological inflammation and oxidative stress, Aß deposition, and tau phosphorylation via the regulation of multiple endogenous metabolic pathways during pathological AD. The research might provide useful support for the further study of pharmacology and new drug development of lignans in S. chinensis.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Lignanas/administração & dosagem , Schisandra/química , Doença de Alzheimer/sangue , Doença de Alzheimer/psicologia , Doença de Alzheimer/urina , Animais , Biomarcadores/sangue , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Cognição/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Humanos , Lignanas/química , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Metabolômica , Neurotransmissores/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Plasma/química , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Urina/química
13.
Nervenarzt ; 90(9): 907-913, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31407045

RESUMO

In accordance with the current German dementia guidelines, the dementia biomarkers amyloid beta 42, the tau peptides total tau and phosphorylated tau 181 are recommended for cerebrospinal fluid (CSF)-based diagnostics of dementia. Several studies have clearly shown that determination of the amyloid beta 42 to amyloid beta 40 peptide ratio is superior to the interpretation of amyloid beta 42 alone and should be implemented in the clinical work-up; however, in recent years different studies have presented many other innovative CSF and blood-based biomarkers. Besides CSF-based neurochemical diagnostics of dementia promising novel protocols for the detection of amyloid beta peptides in blood have meanwhile been published, which can currently be used in clinical studies for blood-based early diagnostics of Alzheimer's dementia. Following further validation and assay optimization these blood assays should be available for routine diagnostics in the near future.


Assuntos
Doença de Alzheimer , Biomarcadores , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Humanos
14.
Chem Commun (Camb) ; 55(70): 10424-10427, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31407744

RESUMO

The development of sensitive and reliable fluorescent probes for the early diagnosis of Alzheimer's disease (AD) is highly challenging and plays an important role in achieving effective treatments. Herein, we designed and synthesized an indole-based fluorophore for TTR in human plasma, an important hallmark of AD pathogenesis. This robust and simple fluorescent method allows quantification of TTR in the complex biological matrix.


Assuntos
Doença de Alzheimer/diagnóstico , Corantes Fluorescentes/química , Pré-Albumina/metabolismo , Doença de Alzheimer/sangue , Peptídeos beta-Amiloides/metabolismo , Humanos , Limite de Detecção , Espectrometria de Fluorescência
15.
Neurology ; 93(9): e917-e926, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31366722

RESUMO

OBJECTIVE: To determine the long-term association of hemoglobin levels and anemia with risk of dementia, and explore underlying substrates on brain MRI in the general population. METHODS: Serum hemoglobin was measured in 12,305 participants without dementia of the population-based Rotterdam Study (mean age 64.6 years, 57.7% women). We determined risk of dementia and Alzheimer disease (AD) (until 2016) in relation to hemoglobin and anemia. Among 5,267 participants without dementia with brain MRI, we assessed hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion. RESULTS: During a mean follow-up of 12.1 years, 1,520 individuals developed dementia, 1,194 of whom had AD. We observed a U-shaped association between hemoglobin levels and dementia (p = 0.005), such that both low and high hemoglobin levels were associated with increased dementia risk (hazard ratio [95% confidence interval (CI)], lowest vs middle quintile 1.29 [1.09-1.52]; highest vs middle quintile 1.20 [1.00-1.44]). Overall prevalence of anemia was 6.1%, and anemia was associated with a 34% increased risk of dementia (95% CI 11%-62%) and 41% (15%-74%) for AD. Among individuals without dementia with brain MRI, similar U-shaped associations were seen of hemoglobin with white matter hyperintensity volume (p = 0.03), and structural connectivity (for mean diffusivity, p < 0.0001), but not with presence of cortical and lacunar infarcts. Cerebral microbleeds were more common with anemia. Hemoglobin levels inversely correlated to cerebral perfusion (p < 0.0001). CONCLUSION: Low and high levels of hemoglobin are associated with an increased risk of dementia, including AD, which may relate to differences in white matter integrity and cerebral perfusion.


Assuntos
Doença de Alzheimer/epidemiologia , Anemia/epidemiologia , Infarto Encefálico/epidemiologia , Encéfalo/irrigação sanguínea , Demência/epidemiologia , Hemoglobinas/metabolismo , Doença de Alzheimer/sangue , Doença de Alzheimer/patologia , Anemia/patologia , Encéfalo/patologia , Infarto Encefálico/patologia , Comorbidade , Demência/sangue , Demência/patologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/patologia , Neuroimagem , Prevalência , Fatores de Risco , Soro/metabolismo , Substância Branca/patologia
16.
Pharmacol Biochem Behav ; 185: 172760, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31422081

RESUMO

BACKGROUND: D-amino acids have been recognized as bioactive substances in humans. d-Serine and D-alanine are co-agonists of N-methyl-d-aspartate receptors. Glutamate has been suggested to be involved in the pathophysiology of Alzheimer's disease (AD). This study aimed to explore the roles of amino acids, particularly D-amino acids, in cognitive decline among patients with AD or mild cognitive impairment (MCI). METHODS: We enrolled 144 patients: 20 amnestic MCI, 85 mild AD, 25 moderate AD, and 14 severe AD. Serum levels of amino acids were measured by high performance liquid chromatography and confirmed by D-amino acid oxidase assay. The cognitive function was mainly evaluated by Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog). RESULTS: ADAS-cog total scores were positively correlated with d-serine (r = 0.186, p = 0.026) and D-/Total- serine ratio (r = 0.191, p = 0.022). ADAS-cog behavior scores were negatively correlated with D-glutamate (r = -0.177, p = 0.034) and L-glutamate (r = -0.250, p = 0.003), but positively correlated with D-alanine (r = 0.236, p = 0.005) and D-/Total- alanine ratio (r = 0.252, p = 0.002). Among the 11 tasks of ADAS-cog, D-glutamate and d-serine were correlated with different items respectively, noteworthily in the opposite direction. CONCLUSION: This is the first study suggesting that D-amino acids in blood may be correlated with ADAS-cog in different items and in the opposite direction. Lower D-glutamate and higher D-alanine levels may predict more behavioral symptoms. In summary, D-glutamate, d-serine and D-alanine play different and characteristic roles in AD. Further longitudinal studies are warranted to elucidate the function and interaction of D-amino acids in specific cognitive domains as well as various phases of dementia.


Assuntos
Alanina/sangue , Doença de Alzheimer/sangue , Doença de Alzheimer/psicologia , Disfunção Cognitiva/sangue , Ácido Glutâmico/sangue , Serina/sangue , Idoso , Idoso de 80 Anos ou mais , Sintomas Comportamentais/sangue , Cromatografia Líquida , Cognição/fisiologia , Estudos de Coortes , Estudos Transversais , Dieta , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Taiwan
17.
Cell Mol Neurobiol ; 39(8): 1217-1221, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31297637

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognitive performance; Mild Cognitive Impairment (MCI) is instead an objective decline in cognitive performance that does not reach pathology. Paired immunoglobulin-like type 2 receptor alpha (PILRA) is a cell surface inhibitory receptor that was recently suggested to be involved in AD pathogenesis. In particular, the arginine-to-glycine substitution in position 78 (R78, rs1859788) was shown to be protective against AD. Herpes simplex virus type 1 (HSV-1) infection is suspected as well to be involved in AD. Interestingly, HSV-1 uses PILRA to infect cells, and HSV-1 infects more efficiently PIRLA G78 compared to R78 macrophages. We analyzed PILRA rs1859788 polymorphism and HSV-1 humoral immune responses in AD (n = 61) and MCI patients (n = 48), and in sex and age matched healthy controls (HC; n = 57). The rs1859788 PILRA genotype distribution was similar among AD, MCI and HC; HSV-1 antibody (Ab) titers were increased in AD and MCI compared to HC (p < 0.05 for both comparisons). Notably, HSV-1-specific IgG1 were significantly increased in AD patients carrying PILRA R78 rs1859788 AA than in those carrying G78 AG or GG (p = 0.01 for both comparisons), and the lowest titers of HSV-1-specific IgG1 were observed in rs1859788 GG AD. HSV-1 IgG are increased in AD patients with the protective R78 PILRA genotype. Because in AD patients brain atrophy is inversely correlated with HSV-1-specific IgG titers, results herein suggest a possible link between two important genetic and infective factors suspected to be involved in AD pathogenesis.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/imunologia , Herpesvirus Humano 1/imunologia , Imunoglobulina G/imunologia , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores Imunológicos/genética , Idoso , Doença de Alzheimer/sangue , Doença de Alzheimer/virologia , Anticorpos Antivirais/imunologia , Feminino , Humanos , Imunidade Humoral , Imunoglobulina G/sangue , Masculino
18.
J Neuroinflammation ; 16(1): 145, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299989

RESUMO

BACKGROUND: Increased plasma YKL-40 has been reported in Alzheimer's disease (AD), but its levels in other neurodegenerative diseases are unknown. Here, we aimed to investigate plasma YKL-40 in the spectrum of neurodegenerative dementias. METHODS: YKL-40 was quantified in the plasma of 315 cases, including healthy controls (HC), neurological disease controls (ND), AD, vascular dementia (VaD), frontotemporal dementia (FTD), sporadic Creutzfeldt-Jakob disease (CJD) and Lewy body dementia (LBD). Diagnostic accuracy in the differential diagnostic context and influence of age and gender was assessed. RESULTS: Highest YKL-40 levels were detected in CJD, followed by LBD, VaD, AD, FTD, ND and HC. YKL-40 was associated to age but not to sex. After controlling for age, YKL-40 was significantly elevated in CJD compared to HC (p < 0.001), ND, AD and VaD (p < 0.01) and in LBD compared to HC (p < 0.05). In CJD, YKL-40 concentrations were significantly higher at late disease stages. CONCLUSIONS: Plasma YKL-40 is significantly elevated in CJD regardless of clinical and genetic parameters, with moderate diagnostic accuracy in the discrimination from control cases. Our study discards a potential use of this biomarker in the differential diagnostic context but opens the possibility to be explored as a marker for CJD monitoring.


Assuntos
Doença de Alzheimer/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Síndrome de Creutzfeldt-Jakob/sangue , Demência Vascular/sangue , Demência Frontotemporal/sangue , Doença por Corpos de Lewy/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/sangue
19.
Medicina (Kaunas) ; 55(7)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284484

RESUMO

Vitamin D is a secosteroid hormone regulating the expression of almost 900 genes, and it is involved in the regulation of calcium and phosphate metabolism, immune response, and brain development. Low blood vitamin D levels have been reported in patients affected by various diseases. Despite a large amount of literature data, there is uncertainty surrounding the role of vitamin D as a serum biomarker in Alzheimer's disease (AD) and Parkinson's disease (PD). Indeed, the lack of internationally recognized 25(OH)D3 reference measurement procedures and standard materials in the past led to unstandardized serum total 25(OH)D3 results among research and clinical care laboratories. Thus, most of the literature studies reported unstandardized data, which are of little use and make it difficult to draw conclusions of the role of vitamin D in AD and PD. This review summarizes the extra-skeletal actions of vitamin D, focusing its role in immunomodulation and brain function, and reports the issue of lacking standardized literature data concerning the usefulness of vitamin D as a biomarker in AD and PD.


Assuntos
Vitamina D/fisiologia , Doença de Alzheimer/sangue , Doença de Alzheimer/etiologia , Biomarcadores/análise , Biomarcadores/sangue , Humanos , Doença de Parkinson/sangue , Doença de Parkinson/etiologia , Secoesteroides/metabolismo , Vitamina D/imunologia , Vitamina D/metabolismo , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/fisiopatologia
20.
Clin Biochem ; 72: 64-70, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31319065

RESUMO

OBJECTIVE: Lipid peroxidation constitutes a molecular mechanism involved in early Alzheimer Disease (AD) stages, and artificial neural network (ANN) analysis is a promising non-linear regression model, characterized by its high flexibility and utility in clinical diagnosis. ANN simulates neuron learning procedures and it could provide good diagnostic performances in this complex and heterogeneous disease compared with linear regression analysis. DESIGN AND METHODS: In our study, a new set of lipid peroxidation compounds were determined in urine and plasma samples from patients diagnosed with early Alzheimer Disease (n = 70) and healthy controls (n = 26) by means of ultra-performance liquid chromatography coupled with tandem mass-spectrometry. Then, a model based on ANN was developed to classify groups of participants. RESULTS: The diagnostic performances obtained using an ANN model for each biological matrix were compared with the corresponding linear regression model based on partial least squares (PLS), and with the non-linear (radial and polynomial) support vector machine (SVM) models. Better accuracy, in terms of receiver operating characteristic-area under curve (ROC-AUC), was obtained for the ANN models (ROC-AUC 0.882 in plasma and 0.839 in urine) than for PLS and SVM models. CONCLUSION: Lipid peroxidation and ANN constitute a useful approach to establish a reliable diagnosis when the prognosis is complex, multidimensional and non-linear.


Assuntos
Doença de Alzheimer/diagnóstico , Peroxidação de Lipídeos , Modelos Biológicos , Idoso , Doença de Alzheimer/sangue , Doença de Alzheimer/urina , Biomarcadores/sangue , Biomarcadores/química , Biomarcadores/urina , Feminino , Humanos , Isoprostanos/sangue , Isoprostanos/química , Isoprostanos/urina , Modelos Lineares , Masculino , Análise Multivariada , Prostaglandinas/sangue , Prostaglandinas/química , Prostaglandinas/urina
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