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1.
Cell Prolif ; 53(4): e12787, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32162733

RESUMO

OBJECTIVES: To provide a new research direction for nerve regeneration and strategy for Alzheimer's disease treatment, tetrahedral DNA nanostructures (TDNs)-novel tetrahedral framework nucleic acid molecule nanoparticles (tFNA) that can inhibit the apoptosis of nerve cells are employed in the experiment. MATERIALS AND METHODS: To verify the successful preparation of TDNs, the morphology of TDNs was observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM). The expression of apoptosis-related genes and proteins was investigated by confocal microscope, flow cytometry, PCR and Western blot to detect the impact of TDNs on the Alzheimer's model. And finally, Morris water maze experiment was used to test behavioural changes and Nissl stain was detected to observe the morphology and quantity of neurons in the hippocampus. Immunofluorescence stain was used to observe the Aß stain, and TUNEL dyeing was utilized to observe neuronal apoptosis. RESULTS: In vitro and in vivo experiments confirm that TDNs, in a specific concentration range, have no toxic or side effects on nerve cells, can effectively inhibit apoptosis in an Alzheimer's disease cell model and effectively improve memory and learning ability in a rat model of Alzheimer's disease. CONCLUSIONS: These findings suggest that TDNs may be a promising drug for the treatment of Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , DNA/uso terapêutico , Nanoestruturas/uso terapêutico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/análise , Animais , Apoptose/efeitos dos fármacos , DNA/farmacocinética , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Modelos Moleculares , Nanoestruturas/ultraestrutura , Células PC12 , Ratos , Ratos Sprague-Dawley
2.
Int. j. morphol ; 38(1): 230-234, Feb. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1056427

RESUMO

The hypotheses currently considered the most likely causes of Alzheimer's disease (AD) are amyloid beta peptide deposition in the cerebral cortex and hyperphosphorylation of the Tau protein, with the consequent formation of neurofibrillary tangles. In clinical practice, although not accurate, AD diagnosis is based on the exclusion of other diseases, behavioural assessments and complementary examinations, such as imaging and blood tests. Advances in the field of biotechnology have created exciting prospects for the early detection of AD via biomarker assessment, which is considered a safer and more efficient procedure. Molecules recognised as biomarkers can be expressed in some body fluids, including cerebrospinal fluid, saliva and blood. The presence of amyloid beta peptide and Tau can be confirmed in saliva, which is also an easily and non-invasively collectable material with an accessible cost. The objective was evaluate the concentrations of the t-Tau protein and Ab42 peptide in the saliva of elderly individuals with and without dementia of the AD type Method: The objective of this case-control study, involving a total of 120 individuals, was to analyse whether a correlation exists between variations in the concentrations of the t-Tau and Ab42 biomarkers in the saliva of patients with confirmed AD and individuals in the inclusion group but without AD . We found that t-Tau expression in AD patients is significantly lower than that in individuals without AD, whereas the salivary concentration of Ab42 is higher in patients with AD but not significantly different from that of the group without AD. Conclusion: Thus, we demonstrate the feasibility of using salivary biomarkers as predictive markers for diagnosis of Alzheimer's disease.


Las hipótesis consideradas actualmente como las causas más probables de la enfermedad de Alzheimer (EA) son la deposición de péptido beta amiloide en la corteza cerebral y la hiperfosforilación de la proteína Tau, con la consiguiente formación de ovillos neurofibrilares. En la práctica clínica, aunque no es precisa, el diagnóstico de la EA se basa en la exclusión de otras enfermedades, evaluaciones de comportamiento y exámenes complementarios, como imágenes y análisis de sangre. Los avances en el campo de la biotecnología han creado interesantes perspectivas para la detección temprana de la EA a través de la evaluación de biomarcadores, que se considera un procedimiento más seguro y más eficiente. Las moléculas reconocidas como biomarcadores se pueden expresar en algunos fluidos corporales, incluidos el líquido cerebroespinal, la saliva y la sangre. La presencia del péptido beta amiloide (AB) y la proteína Tau (t-Tau) se puede confirmar en la saliva, que también es un material fácil y no invasivo de recolección con un costo accesible. El objetivo fue evaluar las concentraciones de la proteína t-Tau y el péptido Ab42 en la saliva de las personas de edad avanzada con y sin demencia del tipo de tipo EA. El estudio de casos y controles, se realizó en un total de 120 personas, para analizar si existe una correlación entre las variaciones en las concentraciones de los biomarcadores t-Tau y Ab42 en la saliva de pacientes con EA confirmada e individuos en el grupo de inclusión pero sin AD. Encontramos que la expresión de t-Tau en pacientes con EA es significativamente menor que en individuos sin EA, mientras que la concentración salival de Ab42 es mayor en pacientes con EA pero no significativamente diferente de la del grupo sin la enfermedad . Por lo tanto, se demuestra la viabilidad del uso de biomarcadores salivales como marcadores predictivos para el diagnóstico de la enfermedad de Alzheimer.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Peptídeos beta-Amiloides/metabolismo , Proteínas tau/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Saliva/metabolismo , Saliva/química , Biomarcadores/análise , Biomarcadores/metabolismo , Peptídeos beta-Amiloides/análise , Proteínas tau/análise
3.
Chem Commun (Camb) ; 56(10): 1537-1540, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31922154

RESUMO

Although the underlying cause of Alzheimer's disease (AD) is not known, the extracellular deposition of ß-amyloid (Aß) is considered as a hallmark of AD brains. Evidence has shown the occurrence of d-Asp, isoAsp, and d-Ser residues in Aß, which may be indicative of and/or contribute to the neurodegeneration in AD patients. Herein, we have developed the first high-throughput profiling technique for all 20 isobaric Aß peptide epimers containing Asp, isoAsp, and Ser isomers using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). This new analytical strategy allows the direct detection and identification of all possible Asp, isoAsp, and Ser stereoisomers in Aß, and may contribute to a better understanding of the pathogenesis of AD.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/análise , Doença de Alzheimer/metabolismo , Sequência de Aminoácidos , Peptídeos beta-Amiloides/química , Ácido Aspártico/química , Cromatografia Líquida de Alta Pressão , Humanos , Serina/química , Estereoisomerismo , Espectrometria de Massas em Tandem
4.
PLoS One ; 15(1): e0227618, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923257

RESUMO

Alzheimer's disease (AD) is an ageing-related neurodegenerative disease characterized and diagnosed by deposition of insoluble amyloid-ß (Aß) plaques in the brain. The plaque accumulation in the brain directly affects reduced levels of Aß in cerebrospinal fluid (CSF) and blood, as Aß can freely transport the blood-brain barrier, and clinical investigations have suggested these two biofluids as promising samples for in vitro diagnosis. Given that the human eye structurally resembles the brain and Aß accumulation often observed in the ocular region of AD patients, in this study, we examined aqueous humor Aß as another possible surrogate biomarker. First, using the acute Aß-infused AD mouse model by injecting Aß to the CSF in intracerebroventricular region of normal ICR mice, we investigated whether Aß concentration in the aqueous humor in AD models is positively correlated with the concentration in the CSF. Then, we examined the correlation of aqueous humor Aß levels with increased plaque deposition in the brain and reduced Aß levels in both CSF and blood in adult and aged 5XFAD Alzheimer transgenic mice. Collectively, the synthetic Aß injected into CSF immediately migrate to the aqueous humor, however, the age-dependently reducing pattern of Aß levels in CSF and blood was not observed in the aqueous humor.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Humor Aquoso/metabolismo , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/fisiologia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Humor Aquoso/citologia , Biomarcadores/sangue , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Placa Amiloide
5.
Neurology ; 94(4): e397-e406, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31888974

RESUMO

OBJECTIVE: To determine the temporal sequence of objectively defined subtle cognitive difficulties (Obj-SCD) in relation to amyloidosis and neurodegeneration, the current study examined the trajectories of amyloid PET and medial temporal neurodegeneration in participants with Obj-SCD relative to cognitively normal (CN) and mild cognitive impairment (MCI) groups. METHOD: A total of 747 Alzheimer's Disease Neuroimaging Initiative participants (305 CN, 153 Obj-SCD, 289 MCI) underwent neuropsychological testing and serial amyloid PET and structural MRI examinations. Linear mixed effects models examined 4-year rate of change in cortical 18F-florbetapir PET, entorhinal cortex thickness, and hippocampal volume in those classified as Obj-SCD and MCI relative to CN. RESULT: Amyloid accumulation was faster in the Obj-SCD group than in the CN group; the MCI and CN groups did not significantly differ from each other. The Obj-SCD and MCI groups both demonstrated faster entorhinal cortical thinning relative to the CN group; only the MCI group exhibited faster hippocampal atrophy than CN participants. CONCLUSION: Relative to CN participants, Obj-SCD was associated with faster amyloid accumulation and selective vulnerability of entorhinal cortical thinning, whereas MCI was associated with faster entorhinal and hippocampal atrophy. Findings suggest that Obj-SCD, operationally defined using sensitive neuropsychological measures, can be identified prior to or during the preclinical stage of amyloid deposition. Further, consistent with the Braak neurofibrillary staging scheme, Obj-SCD status may track with early entorhinal pathologic changes, whereas MCI may track with more widespread medial temporal change. Thus, Obj-SCD may be a sensitive and noninvasive predictor of encroaching amyloidosis and neurodegeneration, prior to frank cognitive impairment associated with MCI.


Assuntos
Peptídeos beta-Amiloides/análise , Encéfalo/patologia , Disfunção Cognitiva/etiologia , Diagnóstico Precoce , Degeneração Neural/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/diagnóstico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Degeneração Neural/patologia , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons
7.
Chem Commun (Camb) ; 56(14): 2087-2090, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31967623

RESUMO

A dual-emissive tris-heteroleptic ruthenium complex is designed, synthesized and applied for the ratiometric photoluminescent detection of amyloid-ß (Aß) aggregation in both steady and transient states. The Aß aggregation is supported by transmission electron microscopy and confocal laser scanning microscopy analysis. In addition, molecular docking calculations have been performed to gain insights into the interaction mode between the ruthenium complex and Aß fibrils.


Assuntos
Peptídeos beta-Amiloides/análise , Complexos de Coordenação/química , Rutênio/química , Complexos de Coordenação/síntese química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Agregados Proteicos
8.
Chem Commun (Camb) ; 56(4): 583-586, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31830165

RESUMO

In this report, we demonstrate a "V-shaped" NIRF probe PTO-29, which can monitor Aß oligomers with high selectivity. PTO-29 was designed and showed significant response to Aß oligomers in the fluorescence spectral tests and good properties. In vivo imaging results indicate that 4 month APP/PS1 AD mice have higher signals in the brain than age-matched wild type mice.


Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/análise , Corantes Fluorescentes/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Corantes Fluorescentes/farmacologia , Raios Infravermelhos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Modelos Moleculares , Estrutura Molecular , Imagem Óptica
9.
Neurology ; 94(3): e282-e291, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31862783

RESUMO

OBJECTIVE: ß-Amyloid (Aß) pathology is common in patients with probable dementia with Lewy bodies (DLB). However, the pathologic basis and the differential diagnostic performance of Aß PET are not established in DLB. Our objective was to investigate the pathologic correlates of 11C-Pittsburgh compound B(PiB) uptake on PET in cases with antemortem diagnosis of probable DLB or Lewy body disease (LBD) at autopsy. METHODS: Autopsied cases who underwent antemortem PiB-PET and were assigned a clinical diagnosis of probable DLB or LBD at autopsy were included (n = 39). The primary endpoint was pathologic diagnosis of LBD, Alzheimer disease (AD), or mixed (LBD and AD) pathology; the secondary endpoints included Thal Aß phase and diffuse and neuritic Aß plaques. RESULTS: Lower global cortical PiB standardized uptake value ratio (SUVr) distinguished cases with LBD from cases with AD or mixed pathology with an accuracy of 93%. Greater global cortical PiB SUVr correlated with higher Thal Aß phase (r = 0.75, p ≤ 0.001). Voxel-based analysis demonstrated that Aß pathology relatively spared the occipital lobes in cases with mixed pathology and LBD compared to cases with AD without LBD, in whom the entire cerebral cortex was involved. Global cortical PiB SUVr was associated primarily with the abundance of diffuse Aß plaques in cases with LBD in a multivariable regression model. CONCLUSION: Lower PiB uptake accurately distinguishes cases with LBD from cases with AD or mixed pathology, correlating with the Thal Aß phase. The severity of diffuse Aß pathology is the primary contributor to elevated PiB uptake in LBD. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that lower PiB uptake accurately distinguishes patients with LBD from those with AD or mixed pathology.


Assuntos
Peptídeos beta-Amiloides/análise , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons
10.
Elife ; 82019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31475904

RESUMO

Tau pathology first appears in the transentorhinal and anterolateral entorhinal cortex (alEC) in the aging brain. The transition to Alzheimer's disease (AD) is hypothesized to involve amyloid-ß (Aß) facilitated tau spread through neural connections. We contrasted functional connectivity (FC) of alEC and posteromedial EC (pmEC), subregions of EC that differ in functional specialization and cortical connectivity, with the hypothesis that alEC-connected cortex would show greater tau deposition than pmEC-connected cortex. We used resting state fMRI to measure FC, and PET to measure tau and Aß in cognitively normal older adults. Tau preferentially deposited in alEC-connected cortex compared to pmEC-connected or non-connected cortex, and stronger connectivity was associated with increased tau deposition. FC-tau relationships were present regardless of Aß, although strengthened with Aß. These results provide an explanation for the anatomic specificity of neocortical tau deposition in the aging brain and reveal relationships between normal aging and the evolution of AD.


Assuntos
Envelhecimento/patologia , Córtex Entorrinal/patologia , Vias Neurais/patologia , Proteínas tau/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/análise , Mapeamento Encefálico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Adulto Jovem
11.
ACS Appl Mater Interfaces ; 11(40): 36299-36306, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31514493

RESUMO

A dual-wavelength ratiometric electrochemiluminescence resonance energy transfer (ECL-RET) aptasensor based on the carbon nitride nanosheet (g-C3N4 NS) and metal-organic frameworks (Ru@MOFs) as energy donor-receptor pairs is first designed for the detection of the amyloid-ß (Aß) protein. The cathode ECL of g-C3N4 NS gradually decreased, whereas the anode ECL from Ru@MOF pyramidally enhanced along with the increasing concentration of Aß in a 0.1 M phosphate-buffered saline solution containing 0.1 M S2O82-. Additionally, it is worth noting that 2-amino terephthalic acid from MOF not only can load abundant amounts of luminophor Ru(bpy)32+ but also promote the conversion of more amounts of S2O82- that served as a coreactant accelerator into SO4•-, further enhancing the ECL signal of Ru@MOF. Besides, the ECL intensity from the g-C3N4 NS had a tremendous spectrum overlap with the UV-vis spectrum of Ru@MOF, demonstrating the high-efficiency ECL-RET from g-C3N4 NS to Ru@MOF. According to the ratio of ECL460nm/ECL620nm, the constructed aptasensor for the detection of Aß showed a wide linear range from 10-5 to 500 ng/mL and a low detection limit of 3.9 fg/mL (S/N = 3) with a correction coefficient of 0.9965. The obtained results certified that the dual-wavelength ratiometric ECL sensor could provide a reliable direction and have the potential for application in biosensing and clinical diagnosis fields.


Assuntos
Peptídeos beta-Amiloides/análise , Aptâmeros de Peptídeos/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Transferência de Energia , Medições Luminescentes/métodos , Nanopartículas/química , Nitrilos/química , Estruturas Metalorgânicas , Nanopartículas/ultraestrutura , Reprodutibilidade dos Testes , Rutênio
12.
Int J Mol Sci ; 20(18)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540372

RESUMO

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia. The disease progression is associated with the build-up of amyloid plaques and neurofibrillary tangles in the brain. However, besides the well-defined lesions, the AD-related pathology includes neuroinflammation, compromised energy metabolism, and chronic oxidative stress. Likewise, the blood-brain barrier (BBB) dysfunction is suggested to be a cause and AD consequence. Accordingly, therapeutic targeting of the compromised BBB is a promising disease-modifying approach. We utilized a homozygous triple-transgenic mouse model of AD (3×Tg-AD) to assess the effects of L-norvaline on BBB integrity. We scrutinized the perivascular astrocytes and macrophages by measuring the immunopositive profiles in relation to the presence of ß-amyloid and compare the results with those found in wild-type animals. Typically, 3×Tg-AD mice display astroglia cytoskeletal atrophy, associated with the deposition of ß-amyloid in the endothelia, and declining nitric oxide synthase (NOS) levels. L-norvaline escalated NOS levels, then reduced rates of BBB permeability, amyloid angiopathy, microgliosis, and astrodegeneration, which suggests AD treatment agent efficacy. Moreover, results undergird the roles of astrodegeneration and microgliosis in AD-associated BBB dysfunction and progressive cognitive impairment. L-norvaline self-evidently interferes with AD pathogenesis and presents a potent remedy for angiopathies and neurodegenerative disorders intervention.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Barreira Hematoencefálica/efeitos dos fármacos , Valina/análogos & derivados , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/análise , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Barreira Hematoencefálica/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Angiopatia Amiloide Cerebral/tratamento farmacológico , Angiopatia Amiloide Cerebral/patologia , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Valina/uso terapêutico
13.
Eur J Med Chem ; 181: 111585, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31404860

RESUMO

Brain amyloid deposits have been identified as the main neuropathological hallmarks of Alzheimer's diseases (AD) and intensive efforts have been devoted to develop aggregation inhibitors preventing the formation of toxic oligomeric Aß for therapeutic. In addition, evidence indicates that the formation and accumulation of ß-amyloid plaques probably precede clinical symptoms by around 20 years and imaging of such plaques would be beneficial for early-stage AD detection. In this study, we investigated phenothiazine-based compounds as novel promising theranostic agents for AD. These multifunctional agents exhibited BBB permeability, low neurotoxicity, good bio-stability as well as strong turn-on fluorescence with a Stokes shift upon binding to Aß aggregates. They had metal-chelating property which could delay Aß aggregation and displayed high binding affinity for ß-amyloid aggregates. Moreover, they have been simultaneously applied to perform in vivo near-infrared fluorescence imaging of ß-amyloid plaques in double transgenic AD mouse model, to prevent self-aggregation of Aß monomer from forming toxic oligomers and to protect human neuroblastoma SH-SY5Y cells against Aß-induced toxicity and oxidative stress.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/análise , Fármacos Neuroprotetores/uso terapêutico , Fenotiazinas/uso terapêutico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacocinética , Imagem Óptica , Fenotiazinas/química , Fenotiazinas/farmacocinética , Placa Amiloide/diagnóstico por imagem , Placa Amiloide/tratamento farmacológico , Agregação Patológica de Proteínas/diagnóstico por imagem , Agregação Patológica de Proteínas/metabolismo , Agregação Patológica de Proteínas/prevenção & controle , Nanomedicina Teranóstica
14.
Int J Mol Sci ; 20(16)2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31405021

RESUMO

At present, the prevalence of Alzheimer's disease, a devastating neurodegenerative disorder, is increasing. Although the mechanism of the underlying pathology is not fully uncovered, in the last years, there has been significant progress in its understanding. This includes: Progressive deposition of amyloid ß-peptides in amyloid plaques and hyperphosphorylated tau protein in intracellular as neurofibrillary tangles; neuronal loss; and impaired glucose metabolism. Due to a lack of effective prevention and treatment strategy, emerging evidence suggests that dietary and metabolic interventions could potentially target these issues. The ketogenic diet is a very high-fat, low-carbohydrate diet, which has a fasting-like effect bringing the body into a state of ketosis. The presence of ketone bodies has a neuroprotective impact on aging brain cells. Moreover, their production may enhance mitochondrial function, reduce the expression of inflammatory and apoptotic mediators. Thus, it has gained interest as a potential therapy for neurodegenerative disorders like Alzheimer's disease. This review aims to examine the role of the ketogenic diet in Alzheimer's disease progression and to outline specific aspects of the nutritional profile providing a rationale for the implementation of dietary interventions as a therapeutic strategy for Alzheimer's disease.


Assuntos
Doença de Alzheimer/dietoterapia , Dieta Cetogênica , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/metabolismo , Animais , Dieta Cetogênica/métodos , Humanos , Neuroproteção , Proteínas tau/análise , Proteínas tau/metabolismo
15.
J Biol Regul Homeost Agents ; 33(4): 1073-1084, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31389227

RESUMO

This study used Sprague Dawley (SD) rats with stroke-prone renovascular hypertension (RHRSP) to establish an animal model of hypertensive white matter lesions (WML), so as to explore the brain functions and unusual ß-amyloid (Aß) accumulation in WML. Hypertensive WML and brain dysfunctions were evaluated by measuring the caudal arterial pressure of model rats, and by observing the histomorphological deformations o f the prefrontal lobe, temporal lobe, hippocampus and corpus callosum, as well as by counting of the number of neurons using Hematoxylin and Eosin (H and E) staining, and by evaluating the changes in rat brain functions, including memory and the ability of visual space learning, using the Morris Water Maze Test. In addition, the study discussed the correlation between Aß accumulation and hypertensive WML cognitive impairment by adopting an enzyme-linked immunosorbent assay (ELISA) to detect the level of Aß 1-42, and by detecting the expression of amyloid precursor protein (APP) and Beta-secretase 1 (BACE1) using Western blot. Results of the study showed that at 4 weeks, 8 weeks, 12 weeks and 16 weeks after operation, the blood pressure and brain Aß expression in the rats of the model group notably increased (P less than 0.01), along with deformed and degenerated brain tissues, confirming that the unusual Aß accumulation may participate in the occurrence and development of hypertensive WML as well as the induction of cerebral cognitive decreases.


Assuntos
Peptídeos beta-Amiloides/análise , Encéfalo/fisiopatologia , Hipertensão/patologia , Substância Branca/patologia , Secretases da Proteína Precursora do Amiloide/análise , Precursor de Proteína beta-Amiloide/análise , Animais , Ácido Aspártico Endopeptidases/análise , Ratos , Ratos Sprague-Dawley
16.
Biosens Bioelectron ; 142: 111518, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31326861

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative illness that affects the elderly population worldwide. The definite diagnosis of AD still depends on post-mortem pathological examination of amyloid plaques consisting of amyliod-ß peptides (Aß) fibrils in the brain so far. However, these fibrils are not closely linked to the development of the disease. Alternatively, soluble Aß are believed to be more reliable biomarkers for early diagnosis of AD. Here, we report a simple approach to quantitative detection of soluble Aß species using N-(6-(benzothiazol-2-yl)pyridin-3-yl)-5-(dimethylamino)naphthalene-1-sulfonamide (BPNS) as a ratiometric fluorescence Zn2+ probe. This ratiometric fluorescence assay is based on the competition of soluble Aß with BPNS for Zn2+, that is, soluble Aß species with higher chelation affinity can capture Zn2+ from BPNS‒Zn2+ adduct, thereby reactivating the ratiometric fluorescence response of BPNS. BPNS exhibited perfect linear relationship (R2 = 0.998) in accordance with the concentration of soluble Aß in the presence of Zn2+. The assay possesses strong anti-interference capacity against exogenous agent or the other proteins, thanks to the high selectivity for soluble Aß species. Importantly, this assay can quantitatively detect soluble Aß species from different types of biological fluids, such as artificial cerebrospinal fluid (ACSF), serum, and plasma in half an hour. This assay provides a low-cost, fast, sensitive, and simple approach for quantitative detection of soluble Aß species and may serve as a potential tool for early-stage AD diagnosis.


Assuntos
Peptídeos beta-Amiloides/análise , Técnicas Biossensoriais/métodos , Quelantes/química , Corantes Fluorescentes/química , Naftalenos/química , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Cátions Bivalentes/química , Humanos , Espectrometria de Fluorescência/métodos , Zinco/química
17.
Biosens Bioelectron ; 142: 111517, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31349185

RESUMO

An electrochemiluminescence (ECL) analytical platform was proposed for ultrasensitive detection of amyloid-ß proteins (Aß) based on the ECL resonance energy transfer (ECL-RET). In this work, gold nanoparticles-functionalized graphitic carbon nitride nanosheets (g-C3N4@Au NPs) and palladium nanoparticles-coated Metal organic framework (Pd NPs@NH2-MIL-53) were synthesized, which were as ECL donor and ECL acceptor respectively. A strong cathode ECL emission was obtained from the g-C3N4@Au NPs when used K2S2O8 as its co-reactant. Here, Au NPs not only was used as an accelerator to enhance and stabilize the ECL signal, but also a connector for attaching Aß antibody. In addition, NH2-MIL-53(Al) was selected as a label material for supporting Pd NPs to synergistically increase the intensity and range of UV-visible absorption. The ECL signal of g-C3N4@Au NPs was intensely decreased when the ECL acceptor probe Pd NPs@NH2-MIL-53 was incubated onto the modified GCE by way of the specific recognition. Under the optimal condition, a wide detection range from 10 fg/mL to 50  ng/mL and a low detection limit of 3.4 fg/mL (S/N = 3) were obtained. In consideration of favorable specificity, stability and reproducibility, the proposed method was successfully applied for Aß detection in actual human serum samples and could be a potential analytical tool for sensitive molecular trace detection in clinical analysis.


Assuntos
Peptídeos beta-Amiloides/sangue , Técnicas Biossensoriais/métodos , Grafite/química , Estruturas Metalorgânicas/química , Compostos de Nitrogênio/química , Paládio/química , Peptídeos beta-Amiloides/análise , Anticorpos Imobilizados/química , Técnicas Eletroquímicas/métodos , Transferência de Energia , Humanos , Imunoensaio/métodos , Limite de Detecção , Medições Luminescentes/métodos , Nanopartículas Metálicas/química , Nanoestruturas/química
18.
J Neurol ; 266(9): 2304-2311, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31179518

RESUMO

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are increasingly used to diagnose Alzheimer's disease (AD). However, important methodological and technical remain regarding measurement variability between kit providers and users. We compared the Lumipulse fully automated assays with the manual INNOTEST assays (both from Fujirebio Europe NV, Gent, Belgium) on a clinically representative sample of patients and controls. METHODS: CSF samples of 156 patients were used to quantify Amyloïd Aß1-42 peptide (Aß1-42) and Total-Tau (T-Tau) protein by chemiluminescent enzyme-immunoassay (Lumipulse). Patients were divided into several subgroups: Alzheimer (AD = 44), mild-cognitive impairment (MCI = 23), other dementias (OD = 36), non-dementing neurological conditions (ND = 11), and controls (CTRL = 42). Clinical cut-offs were determined by comparing AD and CTRL with ROC curves for the two markers and their related ratio (T-Tau/Aß1-42). Subgroups of 58 (for phosphorylated-Tau) and 115 samples (for Aß1-42 and T-Tau) were used to evaluate the concordance of this analyzer with the INNOTEST assays. RESULTS: Lumipulse and INNOTEST assays showed good concordance for all markers, but systematic bias was observed justifying the need to redefine new clinical cut-offs. To discriminate AD from CTRL subjects, T-Tau/Aß1-42 ratio was the best biomarker, with a cut-off value of 1.12 (sensitivity 81.8% and specificity 92.9%). Similar clinical performances were observed for the Lumipulse and Innotests assays on the subsample of 115 subjects. CONCLUSIONS: Our results demonstrate that the Lumipulse Aß1-42 and T-Tau assays show good analytical and clinical performances in the context of patient evaluation referred to a memory clinic. Automated analyzers should be preferred for the measurement of CSF AD biomarkers to reduce inter- and intra-laboratory variability.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Técnicas Imunoenzimáticas/métodos , Medições Luminescentes/métodos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/análise , Biomarcadores/análise , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Técnicas Imunoenzimáticas/normas , Medições Luminescentes/normas , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Proteínas tau/análise
19.
Cardiovasc Pathol ; 42: 36-40, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31226598

RESUMO

Amyloid-ß-related angiitis (ABRA), a subtype of cerebral amyloid angiopathy (CAA), is vasculitis occurring in relation to amyloid-ß (Aß) deposition in the walls of intracranial blood vessels. ABRA is presumed to be caused by some immune response to the deposited Aß. An 81-year-old man on oral anticoagulant therapy complained of headache, nausea, and difficulty with standing after a head injury. Head computed tomography revealed subcortical bleeding in the right temporoparietal lobe, and 3 days after admission, magnetic resonance imaging (MRI) showed subarachnoid hemorrhage (SAH) around the hematoma. Cerebral microbleeds, a characteristic of CAA, were not detected on MRI. On worsening of his symptoms, intracranial brain biopsy and hematoma removal were performed. Intraoperative rapid diagnosis with a frozen section suspected vasculitis, which enabled the prompt initiation of steroid therapy. He was pathologically diagnosed with ABRA (granulomatous angiitis) using a formalin-fixed paraffin-embedded section. Vasculitis was prominent around blood vessels in the pia matter covering the cerebrum. In this case, the inflammatory cells seemed to appear via the subarachnoid space following cerebral hemorrhage and SAH. ABRA seemed to be developed by intracranial hemorrhage in this case.


Assuntos
Peptídeos beta-Amiloides/análise , Angiopatia Amiloide Cerebral/patologia , Artérias Cerebrais/patologia , Pia-Máter/irrigação sanguínea , Hemorragia Subaracnóidea/patologia , Vasculite do Sistema Nervoso Central/patologia , Idoso de 80 Anos ou mais , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/tratamento farmacológico , Angiopatia Amiloide Cerebral/metabolismo , Artérias Cerebrais/química , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/efeitos dos fármacos , Glucocorticoides/uso terapêutico , Humanos , Masculino , Prednisolona/uso terapêutico , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/cirurgia , Resultado do Tratamento , Vasculite do Sistema Nervoso Central/diagnóstico por imagem , Vasculite do Sistema Nervoso Central/tratamento farmacológico , Vasculite do Sistema Nervoso Central/metabolismo
20.
Biosens Bioelectron ; 141: 111438, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31254862

RESUMO

Development of a simple, cost-effective and sensitive biosensing strategy is highly desirable to advance the applications in Alzheimer's disease diagnosis. In this paper, we present a simple, label-free and signal-on electrochemiluminescence (ECL) aptasensor for the detection of amyloid-beta (Aß) peptide using luminol as ECL emitter and in-situ generated reactive oxygen species (ROS) as coreactant via catalytic reaction between Cu2+-Aß and the dissolved O2 in the presence of ascorbic acid (AA). Aß16, the binding site of Cu2+ in the monomeric full-length Aß, was used as a model in present study. As a result, this signal-on ECL aptasensor has exhibited favorable analytical performance for Aß16 monomer with a linear range of 1.0 × 10-13 mol/L-1.0 × 10-8 mol/L and a limit of detection of 3.5 × 10-14 mol/L (S/N=3). Furthermore, the proposed biosensor was also able to detect the full length Aß40 not only in the phosphate buffer saline (PBS) solution but also in human serum. The presented biosensor represents a promising, simple, turn-on and label-free diagnostic tool for blood analysis.


Assuntos
Peptídeos beta-Amiloides/sangue , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Fragmentos de Peptídeos/sangue , Peptídeos beta-Amiloides/análise , Cobre/química , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção , Substâncias Luminescentes/química , Medições Luminescentes/métodos , Luminol/química , Fragmentos de Peptídeos/análise
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