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[PMID]:29429161
[Au] Autor:Li L; Duan XJ; Sun Y; Lu Y; Xu HY; Wang QZ; Wang HY
[Ad] Endereço:Department of Pathology, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China.
[Ti] Título:[Classification of cardiac amyloidosis: an immunohistochemical analysis].
[So] Source:Zhonghua Bing Li Xue Za Zhi;47(2):105-109, 2018 Feb 08.
[Is] ISSN:0529-5807
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To evaluate the sensitivity and specificity of immunohistochemistry (IHC) in the classification of cardiac amyloidosis on endomyocardial biopsy (EMB) and heart allograft. Twenty cardiac tissues from 19 patients at Fuwai Hospital from January, 1990 to April, 2017 with histopathologic features of amyloidosis and Congo red staining positivity were included. IHC was performed with monoclonal antibodies against AA amyloid and polyclonal antibodies against transthyretin (ATTR), λ-light chain (AL-λ), κ-light chain (AL-κ), ApoAâ… , ApoAâ…¡, ApoA â…£ and ß(2)-microglobin. The extent of interstitial staining was evaluated by light microscopy, and three patterns were recognized; these included diffuse pericellular pattern, discrete pericellular pattern, and nodular pattern. Two patterns of vascular deposition were also noted, including arterial pattern and venous pattern. Endocardial involvement was also assessed and recorded. Nineteen cases were divided into three groups according to the pattern of proteins expression in specimens. The first group (5 cases) only showed single protein expression on EMB. The second group (6 cases) showed more than one protein expression, but one of them was intensely stained or any staining of any protein together with ApoA â…£ co-staining. The third group (8 cases) also showed more than one protein expression and all of them had intense staining. Amyloid deposits were successfully subtyped as AL-λ, ATTR, AL-κ and ApoAâ… by IHC in the former two groups with the sensitivity of 11/19. In the third group, amyloid deposits could not be subtyped by immunohistochemistry due to their poor specificity. The pericellular pattern tended to favor AL over ATTR amyloidosis and vascular deposition tended to favor ATTR. Amyloid deposits can be reliably subtyped in diagnostic cardiac specimens using IHC. The co-deposition of chaperon proteins, the distribution of amyloid proteins and clinical features are also auxiliary to subtype cardiac amyloidosis.
[Mh] Termos MeSH primário: Amiloidose/patologia
Cardiomiopatias/patologia
[Mh] Termos MeSH secundário: Amiloide/análise
Neuropatias Amiloides Familiares/patologia
Anticorpos Monoclonais/análise
Apolipoproteína A-I/análise
Apolipoproteínas A/análise
Biópsia
Seres Humanos
Cadeias kappa de Imunoglobulina/análise
Cadeias lambda de Imunoglobulina/análise
Imuno-Histoquímica
Placa Amiloide/patologia
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (APOA1 protein, human); 0 (Amyloid); 0 (Antibodies, Monoclonal); 0 (Apolipoprotein A-I); 0 (Apolipoproteins A); 0 (Immunoglobulin kappa-Chains); 0 (Immunoglobulin lambda-Chains); 0 (apolipoprotein A-IV)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0529-5807.2018.02.005


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[PMID]:28467708
[Au] Autor:Watanabe H; Ono M; Ariyoshi T; Katayanagi R; Saji H
[Ad] Endereço:Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
[Ti] Título:Novel Benzothiazole Derivatives as Fluorescent Probes for Detection of ß-Amyloid and α-Synuclein Aggregates.
[So] Source:ACS Chem Neurosci;8(8):1656-1662, 2017 08 16.
[Is] ISSN:1948-7193
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Deposits of ß-amyloid (Aß) and α-synuclein (α-syn) are the hallmark of Alzheimer's disease (AD) and Parkinson's disease (PD), respectively. The detection of these protein aggregates with fluorescent probes is particularly of interest for preclinical studies using fluorescence microscopy on human brain tissue. In this study, we newly designed and synthesized three push-pull benzothiazole (PP-BTA) derivatives as fluorescent probes for detection of Aß and α-syn aggregates. Fluorescence intensity of all PP-BTA derivatives significantly increased upon binding to Aß(1-42) and α-syn aggregates in solution. In in vitro saturation binding assays, PP-BTA derivatives demonstrated affinity for both Aß(1-42) (K = 40-148 nM) and α-syn (K = 48-353 nM) aggregates. In particular, PP-BTA-4 clearly stained senile plaques composed of Aß aggregates in the AD brain section. Moreover, it also labeled Lewy bodies composed of α-syn aggregates in the PD brain section. These results suggest that PP-BTA-4 may serve as a promising fluorescent probe for the detection of Aß and α-syn aggregates.
[Mh] Termos MeSH primário: Peptídeos beta-Amiloides/metabolismo
Benzotiazóis
Encéfalo/metabolismo
Encéfalo/patologia
Corantes Fluorescentes
Fragmentos de Peptídeos/metabolismo
alfa-Sinucleína/metabolismo
[Mh] Termos MeSH secundário: Idoso
Doença de Alzheimer/metabolismo
Doença de Alzheimer/patologia
Benzotiazóis/síntese química
Benzotiazóis/química
Feminino
Corantes Fluorescentes/síntese química
Corantes Fluorescentes/química
Seres Humanos
Imuno-Histoquímica
Corpos de Lewy/metabolismo
Corpos de Lewy/patologia
Masculino
Estrutura Molecular
Doença de Parkinson/metabolismo
Doença de Parkinson/patologia
Placa Amiloide/metabolismo
Placa Amiloide/patologia
Ligação Proteica
Soluções
Espectrometria de Fluorescência
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Benzothiazoles); 0 (Fluorescent Dyes); 0 (Peptide Fragments); 0 (SNCA protein, human); 0 (Solutions); 0 (alpha-Synuclein); 0 (amyloid beta-protein (1-42))
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1021/acschemneuro.6b00450


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[PMID]:28453930
[Au] Autor:R Cardoso B; Hare DJ; Lind M; McLean CA; Volitakis I; Laws SM; Masters CL; Bush AI; Roberts BR
[Ad] Endereço:The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
[Ti] Título:The APOE ε4 Allele Is Associated with Lower Selenium Levels in the Brain: Implications for Alzheimer's Disease.
[So] Source:ACS Chem Neurosci;8(7):1459-1464, 2017 07 19.
[Is] ISSN:1948-7193
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The antioxidant activity of selenium, which is mainly conferred by its incorporation into dedicated selenoproteins, has been suggested as a possible neuroprotective approach for mitigating neuronal loss in Alzheimer's disease. However, there is inconsistent information with respect to selenium levels in the Alzheimer's disease brain. We examined the concentration and cellular compartmentalization of selenium in the temporal cortex of Alzheimer's disease and control brain tissue. We found that Alzheimer's disease was associated with decreased selenium concentration in both soluble (i.e., cytosolic) and insoluble (i.e., plaques and tangles) fractions of brain homogenates. The presence of the APOE ε4 allele correlated with lower total selenium levels in the temporal cortex and a higher concentration of soluble selenium. Additionally, we found that age significantly contributed to lower selenium concentrations in the peripheral membrane-bound and vesicular fractions. Our findings suggest a relevant interaction between APOE ε4 and selenium delivery into brain, and show changes in cellular selenium distribution in the Alzheimer's disease brain.
[Mh] Termos MeSH primário: Doença de Alzheimer/genética
Doença de Alzheimer/metabolismo
Apolipoproteína E4/genética
Química Encefálica/genética
Selênio/análise
Lobo Temporal/química
[Mh] Termos MeSH secundário: Idoso
Envelhecimento/genética
Envelhecimento/metabolismo
Citosol/química
Feminino
Heterozigoto
Seres Humanos
Masculino
Espectrometria de Massas
Emaranhados Neurofibrilares/química
Placa Amiloide/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Apolipoprotein E4); H6241UJ22B (Selenium)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1021/acschemneuro.7b00014


  4 / 4021 MEDLINE  
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Registro de Ensaios Clínicos
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[PMID]:29365294
[Au] Autor:Honig LS; Vellas B; Woodward M; Boada M; Bullock R; Borrie M; Hager K; Andreasen N; Scarpini E; Liu-Seifert H; Case M; Dean RA; Hake A; Sundell K; Poole Hoffmann V; Carlson C; Khanna R; Mintun M; DeMattos R; Selzler KJ; Siemers E
[Ad] Endereço:From the Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York (L.S.H.); Gérontopôle, Centre Hospitalier Universitaire Toulouse, Unité Mixte de Recherche INSERM Unité 1027 Université Toulouse III-Paul Sabatier
[Ti] Título:Trial of Solanezumab for Mild Dementia Due to Alzheimer's Disease.
[So] Source:N Engl J Med;378(4):321-330, 2018 01 25.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Alzheimer's disease is characterized by amyloid-beta (Aß) plaques and neurofibrillary tangles. The humanized monoclonal antibody solanezumab was designed to increase the clearance from the brain of soluble Aß, peptides that may lead to toxic effects in the synapses and precede the deposition of fibrillary amyloid. METHODS: We conducted a double-blind, placebo-controlled, phase 3 trial involving patients with mild dementia due to Alzheimer's disease, defined as a Mini-Mental State Examination (MMSE) score of 20 to 26 (on a scale from 0 to 30, with higher scores indicating better cognition) and with amyloid deposition shown by means of florbetapir positron-emission tomography or Aß1-42 measurements in cerebrospinal fluid. Patients were randomly assigned to receive solanezumab at a dose of 400 mg or placebo intravenously every 4 weeks for 76 weeks. The primary outcome was the change from baseline to week 80 in the score on the 14-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog14; scores range from 0 to 90, with higher scores indicating greater cognitive impairment). RESULTS: A total of 2129 patients were enrolled, of whom 1057 were assigned to receive solanezumab and 1072 to receive placebo. The mean change from baseline in the ADAS-cog14 score was 6.65 in the solanezumab group and 7.44 in the placebo group, with no significant between-group difference at week 80 (difference, -0.80; 95% confidence interval, -1.73 to 0.14; P=0.10). As a result of the failure to reach significance with regard to the primary outcome in the prespecified hierarchical analysis, the secondary outcomes were considered to be descriptive and are reported without significance testing. The change from baseline in the MMSE score was -3.17 in the solanezumab group and -3.66 in the placebo group. Adverse cerebral edema or effusion lesions that were observed on magnetic resonance imaging after randomization occurred in 1 patient in the solanezumab group and in 2 in the placebo group. CONCLUSIONS: Solanezumab at a dose of 400 mg administered every 4 weeks in patients with mild Alzheimer's disease did not significantly affect cognitive decline. (Funded by Eli Lilly; EXPEDITION3 ClinicalTrials.gov number, NCT01900665 .).
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Anticorpos Monoclonais Humanizados/uso terapêutico
Imunoterapia
[Mh] Termos MeSH secundário: Atividades Cotidianas
Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/diagnóstico
Doença de Alzheimer/psicologia
Peptídeos beta-Amiloides/líquido cefalorraquidiano
Anticorpos Monoclonais Humanizados/efeitos adversos
Biomarcadores/líquido cefalorraquidiano
Método Duplo-Cego
Feminino
Seres Humanos
Infusões Intravenosas
Masculino
Testes de Estado Mental e Demência
Meia-Idade
Fragmentos de Peptídeos/líquido cefalorraquidiano
Placa Amiloide/tratamento farmacológico
Tomografia por Emissão de Pósitrons
Falha de Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Antibodies, Monoclonal, Humanized); 0 (Biomarkers); 0 (Peptide Fragments); 0 (amyloid beta-protein (1-42)); 5D6PWO0333 (solanezumab)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180125
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1705971


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[PMID]:27770234
[Au] Autor:Koss DJ; Jones G; Cranston A; Gardner H; Kanaan NM; Platt B
[Ad] Endereço:School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK. d.koss@abdn.ac.uk.
[Ti] Título:Soluble pre-fibrillar tau and ß-amyloid species emerge in early human Alzheimer's disease and track disease progression and cognitive decline.
[So] Source:Acta Neuropathol;132(6):875-895, 2016 Dec.
[Is] ISSN:1432-0533
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Post-mortem investigations of human Alzheimer's disease (AD) have largely failed to provide unequivocal evidence in support of the original amyloid cascade hypothesis, which postulated deposition of ß-amyloid (Aß) aggregates to be the cause of a demented state as well as inductive to tau neurofibrillary tangles (NFTs). Conflicting evidence suggests, however, that Aß plaques and NFTs, albeit to a lesser extent, are present in a substantial subset of non-demented individuals. Hence, a range of soluble tau and Aß species has more recently been implicated as the disease-relevant toxic entities. Despite the incorporation of soluble proteins into a revised amyloid cascade hypothesis, a detailed characterization of these species in the context of human AD onset, progression and cognitive decline has been lacking. Here, lateral temporal lobe samples (Brodmann area 21) of 46 human cases were profiled via tau and Aß Western blot and native state dot blot protocols. Elevations in phospho-tau (antibodies: CP13, AT8 and PHF-1), pathological tau conformations (MC-1) and oligomeric tau (TOC1) agreed with medical diagnosis (non-AD cf. AD) and Braak stage classification (low, intermediate and high), alongside elevations in soluble Aß species (MOAB-2 and pyro-glu Aß) and a decline in levels of the amyloid precursor protein. Strong correlations were observed between individual Braak stages and multiple cognitive measures with all tau markers as well as total soluble Aß. In contrast to previous reports, SDS-stable Aß oligomers (*56) were not found to be reliable for all classifications and appeared likely to be a technical artefact. Critically, the robust predictive value of total soluble Aß was dependent on native state quantification. Elevations in tau and Aß within soluble fractions (Braak stage 2-3 cf. 0) were evident earlier than previously established in fibril-focused disease progression scales. Together, these data provide strong evidence that soluble forms of tau and Aß co-localise early in AD and are closely linked to disease progression and cognitive decline.
[Mh] Termos MeSH primário: Doença de Alzheimer/metabolismo
Doença de Alzheimer/patologia
Encéfalo/metabolismo
Transtornos Cognitivos/metabolismo
Placa Amiloide/metabolismo
Proteínas tau/metabolismo
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Autopsia
Estudos de Coortes
Progressão da Doença
Feminino
Seres Humanos
Masculino
Emaranhados Neurofibrilares/metabolismo
Emaranhados Neurofibrilares/patologia
Testes Neuropsicológicos
Placa Amiloide/patologia
Escalas de Graduação Psiquiátrica
Estatísticas não Paramétricas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (tau Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180131
[Lr] Data última revisão:
180131
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE


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[PMID]:27776263
[Au] Autor:Cattaneo A; Cattane N; Galluzzi S; Provasi S; Lopizzo N; Festari C; Ferrari C; Guerra UP; Paghera B; Muscio C; Bianchetti A; Volta GD; Turla M; Cotelli MS; Gennuso M; Prelle A; Zanetti O; Lussignoli G; Mirabile D; Bellandi D; Gentile S; Belotti G; Villani D; Harach T; Bolmont T; Padovani A; Boccardi M; Frisoni GB; INDIA-FBP Group
[Ad] Endereço:Biological Psychiatry Laboratory, IRCCS Fatebenefratelli, Brescia, Italy; King's College London, Institute of Psychiatry, London, UK. Electronic address: acattaneo@fatebenefratelli.eu.
[Ti] Título:Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly.
[So] Source:Neurobiol Aging;49:60-68, 2017 Jan.
[Is] ISSN:1558-1497
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The pathway leading from amyloid-ß deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1ß, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-α]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy-) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1ß) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = -9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy- (FC = -7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1ß, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = -0.48, p < 0.001; rho = -0.25, p = 0.024; rho = -0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.
[Mh] Termos MeSH primário: Doença de Alzheimer/etiologia
Transtornos Cognitivos/etiologia
Microbioma Gastrointestinal/fisiologia
Inflamação/etiologia
Intestinos/microbiologia
[Mh] Termos MeSH secundário: Idoso
Doença de Alzheimer/metabolismo
Peptídeos beta-Amiloides/metabolismo
Encéfalo/metabolismo
Transtornos Cognitivos/metabolismo
Citocinas/metabolismo
Feminino
Seres Humanos
Inflamação/metabolismo
Mediadores da Inflamação/metabolismo
Masculino
Meia-Idade
Placa Amiloide/etiologia
Placa Amiloide/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Cytokines); 0 (Inflammation Mediators)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:29216448
[Au] Autor:Huynh TV; Liao F; Francis CM; Robinson GO; Serrano JR; Jiang H; Roh J; Finn MB; Sullivan PM; Esparza TJ; Stewart FR; Mahan TE; Ulrich JD; Cole T; Holtzman DM
[Ad] Endereço:Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Medical Scientist Training Program (MSTP), Washington University School of Medicine, St. Louis, MO 63110, USA.
[Ti] Título:Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of ß-amyloidosis.
[So] Source:Neuron;96(5):1013-1023.e4, 2017 Dec 06.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer disease. Previous studies suggest that reduction of apoE levels through genetic manipulation can reduce Aß pathology. However, it is not clear how reduction of apoE levels after birth would affect amyloid deposition. We utilize an antisense oligonucleotide (ASO) to reduce apoE expression in the brains of APP/PS1-21 mice homozygous for the APOE-ε4 or APOE-ε3 allele. ASO treatment starting after birth led to a significant decrease in Aß pathology when assessed at 4 months. Interestingly, ASO treatment starting at the onset of amyloid deposition led to an increase in Aß plaque size and a reduction in plaque-associated neuritic dystrophy with no change in overall plaque load. These results suggest that lowering apoE levels prior to plaque deposition can strongly affect the initiation of Aß pathology while lowering apoE after Aß seeding modulates plaque size and toxicity.
[Mh] Termos MeSH primário: Peptídeos beta-Amiloides
Amiloidose/tratamento farmacológico
Apolipoproteínas E/antagonistas & inibidores
Oligonucleotídeos Antissenso/uso terapêutico
[Mh] Termos MeSH secundário: Envelhecimento/fisiologia
Alelos
Doença de Alzheimer/patologia
Precursor de Proteína beta-Amiloide/biossíntese
Precursor de Proteína beta-Amiloide/genética
Amiloidose/patologia
Animais
Apolipoproteína E3/genética
Apolipoproteína E4/genética
Seres Humanos
Masculino
Camundongos
Camundongos Transgênicos
Placa Amiloide/patologia
Placa Amiloide/prevenção & controle
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Amyloid beta-Protein Precursor); 0 (Apolipoprotein E3); 0 (Apolipoprotein E4); 0 (Apolipoproteins E); 0 (Oligonucleotides, Antisense)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE


  8 / 4021 MEDLINE  
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[PMID]:29176903
[Au] Autor:Chu TH; Cummins K; Sparling JS; Tsutsui S; Brideau C; Nilsson KPR; Joseph JT; Stys PK
[Ad] Endereço:Hotchkiss Brain Institute, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
[Ti] Título:Axonal and myelinic pathology in 5xFAD Alzheimer's mouse spinal cord.
[So] Source:PLoS One;12(11):e0188218, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:As an extension of the brain, the spinal cord has unique properties which could allow us to gain a better understanding of CNS pathology. The brain and cord share the same cellular components, yet the latter is simpler in cytoarchitecture and connectivity. In Alzheimer's research, virtually all focus is on brain pathology, however it has been shown that transgenic Alzheimer's mouse models accumulate beta amyloid plaques in spinal cord, suggesting that the cord possesses the same molecular machinery and conditions for plaque formation. Here we report a spatial-temporal map of plaque load in 5xFAD mouse spinal cord. We found that plaques started to appear at 11 weeks, then exhibited a time dependent increase and differential distribution along the cord. More plaques were found in cervical than other spinal levels at all time points examined. Despite heavy plaque load at 6 months, the number of cervical motor neurons in 5xFAD mice is comparable to wild type littermates. On detailed microscopic examination, fine beta amyloid-containing and beta sheet-rich thread-like structures were found in the peri-axonal space of many axons. Importantly, these novel structures appear before any plaque deposits are visible in young mice spinal cord and they co-localize with axonal swellings at later stages, suggesting that these thread-like structures might represent the initial stages of plaque formation, and could play a role in axonal damage. Additionally, we were able to demonstrate increasing myelinopathy in aged 5xFAD mouse spinal cord using the lipid probe Nile Red with high resolution. Collectively, we found significant amyloid pathology in grey and white matter of the 5xFAD mouse spinal cord which indicates that this structure maybe a useful platform to study mechanisms of Alzheimer's pathology and disease progression.
[Mh] Termos MeSH primário: Doença de Alzheimer/patologia
Axônios/patologia
Bainha de Mielina/patologia
Medula Espinal/patologia
[Mh] Termos MeSH secundário: Envelhecimento
Precursor de Proteína beta-Amiloide/metabolismo
Animais
Substância Cinzenta/patologia
Seres Humanos
Camundongos Transgênicos
Neurônios Motores/patologia
Neuroglia/patologia
Placa Amiloide/patologia
Substância Branca/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Protein Precursor)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188218


  9 / 4021 MEDLINE  
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[PMID]:27771383
[Au] Autor:Hui J; Feng G; Zheng C; Jin H; Jia N
[Ad] Endereço:Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76# West Yanta Road, Xi'an, Shaanxi 710061, China; Department of Emergency Surgery, Ankang City Central Hospital, 85# Jinzhou Street, Ankang, Shaanxi 725000, Chin
[Ti] Título:Maternal separation exacerbates Alzheimer's disease-like behavioral and pathological changes in adult APPswe/PS1dE9 mice.
[So] Source:Behav Brain Res;318:18-23, 2017 02 01.
[Is] ISSN:1872-7549
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Alzheimer's disease (AD), the most common neurodegenerative disorder that gradually destroys memory and cognitive abilities in the elderly, makes a huge emotional and economic burden on the patients and their families. The presence of senile plaques and the loss of cholinergic neurons in the brain are two neuropathological hallmarks of AD. Maternal separation (MS) is an animal paradigm designed to make early life stress. Studies on wild type rodents showed that MS could induce AD-like cognitive deficit and pathological changes. However, the effects of MS on AD susceptible population or AD animal models are still unclear. In the present study, male APPswe/PS1dE9 transgenic mice were separated from dam and pups 3h per day from postnatal day 2 to day 21. After weaning, all animals were housed under normal conditions (4 mice per cage). At 9-month age, MWM tests were performed to evaluate the learning and memory abilities. Then the pathological changes in the brain were measured by histology staining. The results showed MS mice had more severe deficit of learning and memory. Compared to the control, there were more senile plaques in cortex and hippocampus, fewer cholinergic neurons in nucleus basalis of Meynert in MS mice. These results indicate that MS exacerbates Alzheimer's disease-like behavioral and pathological changes in APPswe/PS1dE9 mice.
[Mh] Termos MeSH primário: Doença de Alzheimer/patologia
Doença de Alzheimer/psicologia
Neurônios Colinérgicos/patologia
Privação Materna
Placa Amiloide/patologia
[Mh] Termos MeSH secundário: Doença de Alzheimer/genética
Precursor de Proteína beta-Amiloide/genética
Animais
Núcleo Basal de Meynert/patologia
Córtex Cerebral/patologia
Hipocampo/patologia
Masculino
Aprendizagem em Labirinto
Memória
Camundongos
Camundongos Transgênicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Protein Precursor)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171202
[Lr] Data última revisão:
171202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE


  10 / 4021 MEDLINE  
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[PMID]:28983039
[Au] Autor:Pospich S; Raunser S
[Ad] Endereço:Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
[Ti] Título:The molecular basis of Alzheimer's plaques.
[So] Source:Science;358(6359):45-46, 2017 10 06.
[Is] ISSN:1095-9203
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Doença de Alzheimer
Placa Amiloide
[Mh] Termos MeSH secundário: Peptídeos beta-Amiloides
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Nm] Nome de substância:
0 (Amyloid beta-Peptides)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE
[do] DOI:10.1126/science.aap8002



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