American journal of neurodegenerative disease最新文献_第9页

Alzheimer's disease biomarkers in animal models: closing the translational gap. 动物模型中的阿尔茨海默病生物标志物:缩小翻译差距。

American journal of neurodegenerative disease Pub Date : 2013-06-21 Print Date: 2013-01-01

Jonathan J Sabbagh, Jefferson W Kinney, Jeffrey L Cummings

{"title":"Alzheimer's disease biomarkers in animal models: closing the translational gap.","authors":"Jonathan J Sabbagh, Jefferson W Kinney, Jeffrey L Cummings","doi":"","DOIUrl":"","url":null,"abstract":"The rising prevalence of Alzheimer's disease (AD) is rapidly becoming one of the largest health and economic challenges in the world. There is a growing need for the development and implementation of reliable biomarkers for AD that can be used to assist in diagnosis, inform disease progression, and monitor therapeutic efficacy. Preclinical models permit the evaluation of candidate biomarkers and assessment of pipeline agents before clinical trials are initiated and provide a translational opportunity to advance biomarker discovery. Fast and inexpensive data can be obtained from examination of peripheral markers, though they currently lack the sensitivity and consistency of imaging techniques such as MRI or PET. Plasma and cerebrospinal fluid (CSF) biomarkers in animal models can assist in development and implementation of similar approaches in clinical populations. These biomarkers may also be invaluable in decisions to advance a treatment to human testing. Longitudinal studies in AD models can determine initial presentation and progression of biomarkers that may also be used to evaluate disease-modifying efficacy of drugs. The refinement of biomarker approaches in preclinical systems will not only aid in drug development, but may facilitate diagnosis and disease monitoring in AD patients. ","PeriodicalId":72170,"journal":{"name":"American journal of neurodegenerative disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703123/pdf/ajnd0002-0108.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31572216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical outcomes and serum uric acid levels in elderly patients with amyotrophic lateral sclerosis aged ≥ 70 years. ≥70岁老年肌萎缩侧索硬化症患者的临床结局和血清尿酸水平

American journal of neurodegenerative disease Pub Date : 2013-06-21 Print Date: 2013-01-01

Hiroshi Kataoka, Takao Kiriyama, Yasuyo Kobayashi, Hirosei Horikawa, Satoshi Ueno

{"title":"Clinical outcomes and serum uric acid levels in elderly patients with amyotrophic lateral sclerosis aged ≥ 70 years.","authors":"Hiroshi Kataoka, Takao Kiriyama, Yasuyo Kobayashi, Hirosei Horikawa, Satoshi Ueno","doi":"","DOIUrl":"","url":null,"abstract":"Background: Amyotrophic lateral sclerosis is a slowly progressive fetal neurodegenerative disease in which clinical phenotype and nutritional status are considered prognostic factors. Advanced age has also been reported to carry a poor prognosis in amyotrophic lateral sclerosis. The elderly population is expected to increase in Japan, as well as in other countries in the near future. Whether late-onset amyotrophic lateral sclerosis affects the average lifespan or survival of patients and the nutritional status was related to survival remains an open question.Methods: We studied the survival of elderly 34 patients with clinically definite amyotrophic lateral sclerosis aged ≥ 70 years and investigated serum triglycerides, cholesterol, LDL/HDL ratio, and glucose. Serum uric acid was examined.Results: The average age at respiratory disorders or death as a whole was 77.5 ± 4.3 years. Survival did not differ significantly between different clinical phenotypes or between patients with and those without riluzole usage. Survival differed significantly between patients with and those without other complications. No biochemical parameter is correlated with outcome in this series, including elevated triglyceride or cholesterol levels and an increased LDL/HDL ratio. The survival correlated with the serum uric acid level (r = 0.407, p = 0.017).Conclusions: The onset of amyotrophic lateral sclerosis at ≥ 70 years of age might not be the key determinant of survival in patients with amyotrophic lateral sclerosis.","PeriodicalId":72170,"journal":{"name":"American journal of neurodegenerative disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703126/pdf/ajnd0002-0140.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31571667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tocilizumab infusion therapy normalizes inflammation in sporadic ALS patients. 托珠单抗输注治疗可使散发性ALS患者的炎症恢复正常。

American journal of neurodegenerative disease Pub Date : 2013-06-21 Print Date: 2013-01-01

Milan Fiala, Mathew T Mizwicki, Rachel Weitzman, Larry Magpantay, Norihiro Nishimoto

{"title":"Tocilizumab infusion therapy normalizes inflammation in sporadic ALS patients.","authors":"Milan Fiala, Mathew T Mizwicki, Rachel Weitzman, Larry Magpantay, Norihiro Nishimoto","doi":"","DOIUrl":"","url":null,"abstract":"Patients with sporadic amyotrophic lateral sclerosis (sALS) show inflammation in the spinal cord and peripheral blood. The inflammation is driven by stimulation of macrophages by aggregated superoxide dismutase 1 (SOD1) through caspase1, interleukin 1 (IL1), IL6 and chemokine signaling. Inflammatory gene activation is inhibited in vitro by tocilizumab, a humanized antibody to IL6 receptor (IL6R). Tocilizumab inhibits global interleukin-6 (IL6) signaling, a key mechanism in chronic rheumatoid disorders. Here we studied in vivo baseline inflammatory gene transcription in peripheral blood mononuclear cells (PBMCs) of 10 sALS patients, and the effects of tocilizumab (Actemra(R)) infusions. At baseline, one half of ALS subjects had strong inflammatory activation (Group 1) (8 genes up regulated >4-fold, P<0.05 vs. controls) and the other half (Group 2) had weak activation. All patients showed greater than four-fold up regulation of MMP1, CCL7, CCL13 and CCL24. Tocilizumab infusions in the Group 1 patients resulted in down regulation of inflammatory genes (in particular IL1β), whereas in the Group 2 patients in up regulation of inflammatory genes. Post-infusion serum and CSF concentrations of tocilizumab inhibited caspase1 activation in vitro. Three of 5 patients receiving tocilizumab infusions showed time-limited attenuation of clinical progression. In conclusion, inflammation of sALS patients at baseline is up- or down-regulated in comparison to controls, but is partially normalized by tocilizumab infusions. ","PeriodicalId":72170,"journal":{"name":"American journal of neurodegenerative disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703125/pdf/ajnd0002-0129.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31571666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association between spinocerebellar ataxias caused by glutamine expansion and psychiatric and neuropsychological signals - a literature review. 谷氨酰胺扩张引起的脊髓小脑共济失调与精神和神经心理信号的关系——文献综述。

American journal of neurodegenerative disease Pub Date : 2013-06-21 Print Date: 2013-01-01

Uanda Cristina Almeida-Silva, Jaime Eduardo Cecílio Hallak, Wilson Marques Júnior, Flávia de Lima Osório

{"title":"Association between spinocerebellar ataxias caused by glutamine expansion and psychiatric and neuropsychological signals - a literature review.","authors":"Uanda Cristina Almeida-Silva, Jaime Eduardo Cecílio Hallak, Wilson Marques Júnior, Flávia de Lima Osório","doi":"","DOIUrl":"","url":null,"abstract":"The autosomal dominant cerebellar ataxias, also known as spinocerebellar ataxias (SCA), are characterized by cerebellar degeneration and by their afferent and efferent connections. Currently, at least 31 types of SCA are described, among which a subset, comprising types 1, 2, 3, 6, 7, 17 of the disease, is distinguished due to sharing the same form of mutation involving the repetition of the series of CAG triplets, known as polyglutamine diseases (SCApolyQ). Through a systematic literature review using the Pubmed, PsycoINFO, LILACS and SciELO databases and the keywords Spinocerebellar Ataxia in association with the words neuropsychiatric, psychological, cognitive impairment(s) and psychiatric comorbidities this study aimed to identify the possible associations between SCApolyQ and neuropsychological and psychiatric symptoms/disorders. A greater presence of symptoms of depression and anxiety was evidenced, as well as the existence of cognitive impairments in the patients with SCApolyQ when compared with the general population, with important differences in the profile of these impairments among the types of SCA. It was observed that the findings, in general, indicated greater impairment in the executive functions, verbal fluency and verbal memory and that there was a higher concentration of studies for SCA2 and SCA3. However, there is a need for a greater number of studies using a more homogeneous methodology, which perform direct comparisons between the types of ataxias and that explore some of the still little evaluated neuropsychological functions and the different psychiatric disorders in their amplitude. ","PeriodicalId":72170,"journal":{"name":"American journal of neurodegenerative disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703120/pdf/ajnd0002-0057.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31572212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunity and inflammation in neurodegenerative diseases. 神经退行性疾病的免疫和炎症。

American journal of neurodegenerative disease Pub Date : 2013-06-21 Print Date: 2013-01-01

Giuseppe Cappellano, Miryam Carecchio, Thomas Fleetwood, Luca Magistrelli, Roberto Cantello, Umberto Dianzani, Cristoforo Comi

引用次数: 0

Copper phenotype in Alzheimer's disease: dissecting the pathway. 阿尔茨海默病中的铜表型:解剖通路。

American journal of neurodegenerative disease Pub Date : 2013-06-21 Print Date: 2013-01-01

Rosanna Squitti, Renato Polimanti

{"title":"Copper phenotype in Alzheimer's disease: dissecting the pathway.","authors":"Rosanna Squitti, Renato Polimanti","doi":"","DOIUrl":"","url":null,"abstract":"Alzheimer's disease (AD) is the most common form of dementia. Several hypotheses have been put forward to explain the basis of disease onset and progression. Unfortunately, none of these seems to clarify the complexity of the pathogenesis. In fact, diverse and independent pathogenetic pathways can be disrupted at the same time, and each contributes to disease etiology. In recent years, researchers have begun studying biometals more deeply. A number of studies have shown that metal dyshomeostasis may enhance AD onset and progression. Specifically, different authors have hypothesized that alterations in metal metabolism are associated with an increased in metal-related oxidative stress and beta-amyloid oligomer formation and precipitation. Studies conducted in vivo, in vitro, in living patients and in silico studies have demonstrated that local and systemic defects in copper metabolism are characteristic signs of AD. This strongly supports the hypothesis that copper pathways may be disrupted by the disease. More specifically, a copper phenotype can be proposed for AD, based on defects found in genes involved in copper metabolism. In this review, we describe copper dyshomeostasis in AD patients and attempt to explain the basis of the AD copper phenotype. Dissecting copper pathways, we highlight mechanisms which may be at the basis of the disease. We also discuss various associated translation outcomes. ","PeriodicalId":72170,"journal":{"name":"American journal of neurodegenerative disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703119/pdf/ajnd0002-0046.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31572211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

American journal of neurodegenerative disease Pub Date : 2013-06-21 Print Date: 2013-01-01

Larry D Sparks, Richard J Kryscio, John C Hunsaker

{"title":"Early age-related progression of AD-like neuropathology in Down's syndrome.","authors":"Larry D Sparks, Richard J Kryscio, John C Hunsaker","doi":"","DOIUrl":"","url":null,"abstract":"We have previously reported that increased numbers of Alz-50-reactive (apoptotic) neurons occurred in young DS subjects compared to controls, but increased in density with increasing age, and in advance of identifiable senile plaques (SP) in DS. The purpose of the study was to determine if there are further differences in Alzheimer's disease (AD)-like neuropathology with increasing age among individuals with Down's syndrome (DS) compared to cognitively normal age-matched controls. The two populations compared were age-matched normal controls (N = 14) between 11 months and 61 years of age and individuals with DS (N = 8) between 1 and 54 years of age. There were 7 cognitively intact DS and 10 control subjects under 35 years of age. The single demented 54 year old DS subject was compared to 4 non-demented controls between 48 and 61 years of age. 50 μm Vibratome sections of formalin fixed hippocampal formations were immunohistochemically stained for amyloid-β (6E10), APP (22C11) and phosphorylated tau (AT8) using standard methods. AT8 immunoreactive features were found only in the oldest DS subject. In contrast, the number and intensity of amyloid-β-immunoreactive neurons were maximal in the youngest DS subjects (1-24 years), reduced in the young adults (25-35 years) synchronous with the appearance of only diffuse-form SP, and were further reduced in the 54 year-old DS subject exhibiting abundant multiform SP. Distribution of APP immunoreactivity (22C11) was distinct from amyloid-β (6E10) in appearance and by location and age in both DS and normal controls. The data indicates that the earliest observable neuropathologic feature in DS may be neuronal accumulation of amyloid-β. Such accumulation of amyloid-β occurs decades in advance of deposition as SP, which in turn occurs decades before cognitive decline. ","PeriodicalId":72170,"journal":{"name":"American journal of neurodegenerative disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703124/pdf/ajnd0002-0121.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31572214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiplex assessment of a panel of 16 serum molecules for the differential diagnosis of Alzheimer's disease. 一组16个血清分子对阿尔茨海默病鉴别诊断的多重评估

American journal of neurodegenerative disease Pub Date : 2013-01-01 Epub Date: 2013-03-08

Gloria Biella, Massimo Franceschi, Francesca De Rino, Annalisa Davin, Giacomo Giacalone, Paola Brambilla, Panagiotis Bountris, Maria Haritou, Giuseppe Magnani, Filippo Martinelli Boneschi, Gianluigi Forloni, Diego Albani

{"title":"Multiplex assessment of a panel of 16 serum molecules for the differential diagnosis of Alzheimer's disease.","authors":"Gloria Biella, Massimo Franceschi, Francesca De Rino, Annalisa Davin, Giacomo Giacalone, Paola Brambilla, Panagiotis Bountris, Maria Haritou, Giuseppe Magnani, Filippo Martinelli Boneschi, Gianluigi Forloni, Diego Albani","doi":"","DOIUrl":"","url":null,"abstract":"One of the current challenge in Alzheimer's disease (AD) is the identification of reliable biomarkers that might improve diagnostic accuracy, possibly correlating with the disease progression and patient's response to therapy. As the clinically validated AD biomarkers evaluate cerebrospinal fluid (CSF) parameters, the need for less invasive diagnostic markers is well evident. To this respect, blood circulating cytokines or growth factors have provided some encouraging results, even though no clinically validated to date. In 2007 Ray et al suggested a panel of 18 circulating molecules that might increase AD diagnostic accuracy. In an attempt of replicating their data, we designed a multiplex fluorimetric assay comprising 16 independent analytes and covering 15 out of the 18 described proteins. We collected serum samples from three diagnostic groups: probable AD (n=33), matched healthy controls (CNT, n=23) and non AD demented (NAD, n=14). After correction for age, we found an increased level of EGF-1 in AD in comparison to CNT and NAD, while an increase of TRAIL-R4 was found in NAD. However, evaluation of specificity/sensitivity by ROC curve analysis gave weak evidence of diagnostic accuracy (area under the curve = 0.63 and 0.66 for EGF and TRAIL-R4, respectively). Finally, we tried to find a diagnostic classifier by a multivariate algorithm. We found indication of diagnostic evidence for AD only, while NAD samples did not show a diagnostic pattern.","PeriodicalId":72170,"journal":{"name":"American journal of neurodegenerative disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601470/pdf/ajnd0002-0040.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31323898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Convenient diagnosis of spinal and bulbar muscular atrophy using a microchip electrophoresis system. 利用微芯片电泳系统方便诊断脊髓和球性肌萎缩。

American journal of neurodegenerative disease Pub Date : 2013-01-01 Epub Date: 2013-03-08

Hirofumi Maruyama, Hiroyuki Morino, Yuishin Izumi, Kouichi Noda, Hideshi Kawakami

{"title":"Convenient diagnosis of spinal and bulbar muscular atrophy using a microchip electrophoresis system.","authors":"Hirofumi Maruyama, Hiroyuki Morino, Yuishin Izumi, Kouichi Noda, Hideshi Kawakami","doi":"","DOIUrl":"","url":null,"abstract":"Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive motor neuron disease. Lower and primary sensory neuronopathy is one of the major neuropathological changes that occurs in SBMA. However, many sings are common to SBMA and amyotrophic lateral sclerosis (ALS), and SBMA patients are sometimes diagnosed with ALS. Leuprorelin may be used to treat SBMA, but an accurate diagnosis is necessary for treatment and care. Genetic diagnosis can be performed to detect the expansion of a CAG repeat in the androgen receptor gene in SBMA patients. To screen for this expansion, we used a microchip electrophoresis system. The discrepancy between the actual repeat length and that found by the microchip electrophoresis system was roughly dependent on the repeat length. The mean difference was -6.8 base pairs (bp) in SBMA patients, -0.30 bp in controls. The microchip electrophoresis results were approximately 2 CAG repeats shorter than the actual repeat length in SBMA patients. Using this method, we screened our ALS samples (31 were familial, 271 were sporadic): 4 subjects were diagnosed with SBMA; 2 had familial ALS, and 2 had sporadic ALS (0.7%). The microchip electrophoresis system is semi-quantitative, convenient and useful for screening a large number of samples.","PeriodicalId":72170,"journal":{"name":"American journal of neurodegenerative disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601469/pdf/ajnd0002-0035.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31324002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The impact of DaTscan on the diagnosis and management of movement disorders: A retrospective study. DaTscan对运动障碍诊断和治疗的影响:一项回顾性研究。

American journal of neurodegenerative disease Pub Date : 2013-01-01 Epub Date: 2013-03-08

Kimberly D Seifert, Jonathan I Wiener

引用次数: 0