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Associations of AT(N) biomarkers with neuropsychiatric symptoms in prechnical Alzheimer’s disease and cognitively unimpaired individuals

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Translational Neurodegeneration 2021年第1期10卷 126-139页

作者： Kok Pin Ng Hui Chiew pedro Rosa-neto Nagaendran Kandiah Zahinoor Ismail Serge Gauthier Department of Neurology National Neuroscience InstituteSingaporeSingapore Duke-NUS Medical School SingaporeSingapore Lee Kong Chian School of Medicine-Imperial College London Nanyang Technological UniversitySingaporeSingapore The McGill University Research Centre for Studies in Aging MontrealCanada Hotchkiss Brain Institute and Obrien Institute for Public Health/Departments of Psychiatry Clinical Neurosciencesand Community Health SciencesUniversity of CalgaryCalgaryAlbertaCanada

The development of in vivo biomarkers of Alzheimer's disease(AD)has advanced the diagnosis of AD from a clinical syndrome to a biological *** preclinical stage of AD continuum is defined by the identification of AD biomarkers crossing the pathological threshold in cognitively unimpaired *** neuropsychiatric symptoms(NPS)are non-cognitive symptoms that are increasingly recognized as early manifestations of AD,the associations of NPS with AD pathophysiology in preclinical AD remain ***,we review the associations between NPS and AD biomarkers amyloid-(3(Aβ),tau and neurodegeneration in preclinical AD and cognitivelyunimpaired individuals in 19 eligible English-language publications(8 cross-sectional studies,10 longitudinal,1 both cross-sectional and longitudinal).The cross-sectional studies have consistently shown that NPS,particularly depressive and anxiety symptoms,are associated with higher Aβ.The longitudinal studies have suggested that greater NPS are associated with higher Aβ and cognitive decline in cognitively unimpaired subjects over ***,most of the studies have either cross-sectionally or longitudinally shown no association between NPS and tau *** the association of NPS and neurodegeneration,two studies have shown that the cerebrospinal fluid total-tau is linked to longitudinal increase in NPS and that the NPS may predict longitudinal metabolic decline in preclinical AD,***,evidence for the association between atrophy and NPS in preclinical AD is less ***,future longitudinal studies with well-designed methodologies and NPS measurements are required not only to determine the relationship among AT(N)biomarkers,NPS and cognitive decline,but also to elucidate the contribution of comorbid pathology to preclinical AD.

关键词： Neuropsychiatric symptoms Preclinical Alzheimer's disease Mild behavioral impairment Amyloid-β Hyperphosphorylated tau Neurodegeneration

Prevention strategies for Alzheimer’s disease

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Translational Neurodegeneration 2012年第1期1卷 99-102页

作者： Serge Gauthier Liyong Wu pedro Rosa-neto Jianping Jia McGill Center for studies in Aging McGill UniversityMontrealCanada Neurological Department Xuanwu HospitalCapital UniversityBeijingChina McGill Centre for Studies in Aging(MCSA) McGill University6825Boul.LaSalle BlvdMontrealQC H4H 1R3Canada

Symptomatic treatment during the dementia stage of Alzheimer’s disease(AD)cannot delay or halt the progression of this ***,prevention in the preclinical stage is likely the most effective way to decrease the incidence of this age-associated neurodegenerative condition,and its associated burden for individuals and ***,gender,family history,ApoE4,systolic blood pressure,body mass index,total cholesterol level and physical activity are all used as component of dementia risk *** have been numerous challenges in conducting primary prevention trials in *** strategies for prevention studies include studying those subjects with more risk factors for AD,such as older age,those with a positive family history of late onset AD,and those who are ApoE4 *** of these strategies is designed to increase the probability of developing AD thereby decreasing the sample size or the duration of follow *** strategy would be to target directly the pathophysiology of AD in its preclinical stages and use the biomarkers in prevention trial as surrogate *** will be done first in carriers of dominantly inherited early onset *** this research takes place networks of memory clinics must prepare to transfer new knowledge to persons interested in a preventive approach to AD.

关键词： Alzheimer disease Risk factor Prevention Clinical trial Clinical practice

In vivo tracking of tau pathology using positron emission tomography (PET) molecular imaging in small animals

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Translational Neurodegeneration 2014年第1期3卷 34-39页

作者： Eduardo Rigon Zimmer Antoine Leuzy Venkat Bhat Serge Gauthier pedro Rosa-neto Translational Neuroimaging Laboratory(TNL) McGill Center for Studies in AgingDouglas Mental Health University InstituteMcGill University6875 La Salle Blv-FBC room 3149MontrealQCH4H 1R3Canada Montreal Neurological Institute(MNI) MontrealCanada Department of Biochemistry Federal University of Rio Grande do Sul(UFRGS)Porto AlegreBrazil Department of Psychiatry McGill UniversityMontrealBrazil

Hyperphosphorylation of the tau protein leading to the formation of neurofibrillary tangles(NFTs)is a common feature in a wide range of neurodegenerative diseases known as tauopathies,which include Alzheimer’s disease(AD)and the frontotemporal dementias(FTDs).Although heavily investigated,the mechanisms underlying the pathogenesis and progression of tauopathies have yet to be fully *** this context,several rodent models have been developed that successfully recapitulate the behavioral and neurochemical features of tau pathology,aiming to achieve a better understanding of the link between tau and *** date,behavioral and biochemical parameters assessed using these models have been conducted using a combination of memory tasks and invasive methods such as cerebrospinal fluid(CSF)sampling or post-mortem ***,several novel positron emission tomography(PET)radiopharmaceuticals targeting tau tangles have been developed,allowing for non-invasive in vivo quantification of tau *** with tau transgenic models and micro-PET,these tracers hold the promise of advancing the development of theoretical models and advancing our understanding of the natural history of AD and non-AD *** this review,we briefly describe some of the most important insights for understanding the biological basis of tau pathology,and shed light on the opportunity for improved modeling of tau pathology using a combination of tau-radiopharmaceuticals and animal models.

关键词： Positron emission tomography Tau molecular agents Tau rodent models Tauopathies

Cerebrospinal fluid phosphorylated tau,visinin-like protein-1,and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease

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Translational Neurodegeneration 2018年第1期7卷 221-232页

作者： Hua Zhang Kok Pin Ng Joseph Therriault Min Su Kang Tharick APascoal pedro Rosa-neto Serge Gauthier the Alzheimer’s Disease Neuroimaging Initiative Department of Neurology the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Neurology National Neuroscience InstituteSingaporeSingapore The McGill University Research Centre for Studies in Aging McGill UniversityMontrealCanada 不详

Background:Visinin-like protein-1(VILIP-1)and chitinase-3-like protein 1(CHI3L1 or YKL-40)in cerebrospinal fluid(CSF)are newly discovered markers indicating neuronal damage and microglial activation,*** tau(p-tau)reflects the neuropathology of Alzheimer’s disease(AD)and is useful as diagnostic markers for ***,it is unknown whether these biomarkers have similar or complementary information in ***:We stratified 121 participants from the Alzheimer’s Disease Neuroimaging Initiative(ADNI)database into cognitively normal(CN),stable mild cognitive impairment(sMCI),progressive MCI(pMCI),and dementia due to *** of covariance(ANOVA)and chi-square analyses,Spearman correlation,and logistic regression models were performed to test the demographic,associations between biomarkers,and diagnostic accuracies,*** mixed-effects models were used to evaluate the effects of CSF amyloid-β(Aβ)on above biomarkers within diagnostic groups,the combination of diagnostic group and Aβstatus as predictor,and CSF biomarkers as predictors of AD features,including cognition measured by Mini–Mental State Examination(MMSE)and brain structure and white matter hyperintensity(WMH)measured by magnetic resonance imaging(MRI).Results:P-tau,VILIP-1,and YKL-40 were all predictors of AD diagnosis,but combinations of biomarkers did not improve the diagnostic accuracy(AUC 0.924 for p-tau,VILIP-1,and YKL-40)compared to p-tau(AUC 0.922).P-tau and VILIP-1 were highly correlated(r=0.639,p<0.001)and strongly associated with Aβpathology across clinical stages of AD,while YKL-40 was correlated with Aβpathology in CN and AD ***-1 was associated with acceleration of cognitive decline,hippocampal atrophy,and expansion of ventricles in longitudinal ***-40 was associated with hippocampal atrophy at baseline and follow-up,while p-tau was only associated with worsening WMH at ***:CSF levels of p-tau,VILIP-1,and YKL-40 may have uti

关键词： Alzheimer’s disease Amyloid-β Chitinase-3-like protein 1 Phosphorylated tau Visinin-like protein-1

Nicotinic cholinergic receptors in esophagus:Early alteration during carcinogenesis and prognostic value

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World Journal of Gastroenterology 2016年第31期22卷 7146-7156页

作者： Marina Chianello Nicolau Luis Felipe Ribeiro Pinto pedro Nicolau-neto Paulo Roberto Alves de Pinho Ana Rossini Tatiana de Almeida Simao Sheila Coelho Soares Lima Departamento de Bioquímica Instituto de Biologia Roberto Alcantara GomesUniversidade do Estado do Rio de Janeiro Programa de Carcinogênese Molecular Instituto Nacional de CancerCoordenacao de Pesquisa Gastroenterologia Hospital Universitário Pedro ErnestoUniversidade do Estado do Rio de Janeiro

AIM: To compare expression of nicotinic cholinergic receptors(CHRNs) in healthy and squamous cell carcinoma-affected esophagus and determine the prognostic ***: We performed RT-q PCR to measure the expression of CHRNs in 44 esophageal samples from healthy individuals and in matched normal surrounding mucosa, and in tumors from 28 patientsdiagnosed with esophageal squamous cell carcinoma(ESCC). Next, we performed correlation analysis for the detected expression of these receptors with the habits and clinico-pathological characteristics of all study participants. In order to investigate the possible correlations between the expression of the different CHRN subunits in both healthy esophagus and tissues from ESCC patients, correlation matrices were generated. Subsequently, we evaluated whether the detected alterations in expression of the various CHRNs could precede histopathological modifications during the esophageal carcinogenic processes by using receiver operating characteristic curve analysis. Finally, we evaluated the impact of CHRNA5 and CHRNA7 expression on overall survival by using multivariate ***: CHRNA3, CHRNA5, CHRNA7 and CHRNB4, but not CHRNA1, CHRNA4, CHRNA9 or CHRNA10, were found to be expressed in normal(healthy) esophageal mucosa. In ESCC, CHRNA5 and CHRNA7 were overexpressed as compared with patient-matched surrounding non-tumor mucosa(ESCC-adjacent mucosa; P < 0.0001 and P = 0.0091, respectively). Positive correlations were observed between CHRNA3 and CHRNB4 expression in all samples analyzed. Additionally, CHRNB4 was found to be differentially expressed in the healthy esophagus and the normalappearing ESCC-adjacent mucosa, allowing for distinguishment between these tissues with a sensitivity of 75.86% and a specificity of 78.95%(P = 0.0002). Finally, CHRNA5 expression was identified as an independent prognostic factor in ESCC; patients with high CHRNA5 expression showed an increased overall survival, in comparison with those

关键词： Nicotinic cholinergic receptors Esophagus Esophageal squamous cell carcinoma Tobacco Alcohol Gene expression

Perspective on the use of synthetic biology in rudimentary food fermentations

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Systems Microbiology and Biomanufacturing 2023年第1期3卷 150-165页

作者： Alexander da Silva Vale Gilberto Vinícius de Melo Pereira Leonardo Martins Santana Dão pedro de Carvalho neto Brigitte Sthepani Orozco Colonia Vanete Thomaz Soccol Bruna Leal Maske Carlos Ricardo Soccol Department of Bioprocess Engineering and Biotechnology Federal University of Paraná(UFPR)CuritibaPRBrazil Department of Genetics University of São Paulo(USP)Ribeirão PretoSPBrazil Federal Institute of Education Science and Technology of Paraná(IFPR)LondrinaPRBrazil

Rudimentary food fermentation can be defined as a spontaneous process of conversion of food components through enzy-matic action.A great variety of fermented foods are produced using spontaneous approaches;however,cocoa and coffee represent the most important agricultural commodities on international *** a manner to increase the efficiency of these processes,starter cultures have been developed and applied under field *** selection process begins with the recovery of microbial strains from spontaneous fermentation through phenotypic and metabolic ***,mutation-based breeding is used to develop and improve well-adapted starter *** advances in synthetic biology,especially in the last decade,the development of robust cellular fabrications with high fermentative capacity has become easier-largely due to the development of genomic approaches,such as next-generation sequencing techniques,CRISPR-Cas system and bioinformatics *** review brings prospects on the use of synthetic biology to design new robust strains for use in cocoa and coffee fermentations,but which can be extended to other rudimentary *** addition,metabolic traits and target genes(e.g.,UvrA,RecA,GPD1,and GPP2)are proposed as a starting point for the improvement of cocoa and coffee ***,the regulatory and safety requirements for these food crops are *** review aims to stimulate research on the process of fermentation and the associated synthetic biology tools to produce fermented food efficiently and sustainably.

关键词： Coffee fermentation Cocoa fermentation Starter cultures CRISPR-Cas Synthetic promoters

Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer's disease

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Translational Neurodegeneration 2021年第1期10卷 1-11页

作者： Kok Pin Ng Tharick A.Pascoal Sulantha Mathotaarachchi Yiong Huak Chan Lai Jiang Joseph Therriault Andrea L.Benedet Monica Shin Nagaendran Kandiah Celia M.T.Greenwood pedro Rosa-neto Serge Gauthier Dominantly Inherited Alzheimer Network Alzheimer's Disease Research Unit McGill Centre for Studies in AgingMcGill UniversityMontrealQuebecCanada Translational Neuroimaging Laboratory The McGill University Research Centre for Studies in AgingMontrealCanada Departm ent of Neurology National Neuroscience InstituteSingapore CitySingapore Biostatistics Unit Yong Loo Lin School of MedicineNational University of SingaporeSingapore CitySingapore Lady Davis Institute McGill UniversityMontrealCanada Department of Epidemiology Biostatistics and Occupational HealthMcGill UniversityMontrealCanada 不详

Background:Neuropsychiatric symptoms(NPS)are increasingly recognized as early non-cognitive manifestations in the Alzheimer's disease(AD)***,the role of NPS as an early marker of pathophysiological progression in AD remains *** inherited AD(DIAD)mutation carriers are young individuals who are destined to develop AD in future due to the full penetrance of the genetic ***,the study of DIAD mutation carriers enables the evaluation of the associations between pure AD pathophysiology and metabolic correlates of NPS without the confounding effects of co-existing *** this longitudinal study,we aimed to identify regional brain metabolic dysfunctions associated with NPS in cognitively intact DIAD mutation ***:We stratified 221 cognitively intact participants from the Dominantly Inherited Alzheimer's Network according to their mutation carrier *** interactions of NPS measured by the Neuropsychiatric Inventory-Questionnaire(NPI-Q),age,and estimated years to symptom onset(EYO)as a function of metabolism measured by[^(18)F]flurodeoxyglucose([^(18)F]FDG)positron emission tomography,were evaluated by the mixed-effects regression model with family-level random effects in DIAD mutation carriers and *** factor analysis was performed to identify the neuropsychiatric subsyndromes in DIAD mutation carriers using the NPI-Q *** the effects of interactions between specific neuropsychiatric subsyndromes and EYO on metabolism were evaluated with the mixed-effects regression ***:A total of 119 mutation carriers and 102 non-carriers were *** interaction of higher NPI-Q and shorter EYO was associated with more rapid declines of global and regional[18F]FDG uptake in the posterior cingulate and ventromedial prefrontal cortices,the bilateral parietal lobes and the right insula in DIAD mutation *** neuropsychiatric subsyndromes of agitation,disinhibition,irritability

关键词： Neuropsychiatric symptoms Dominantly inherited Alzheimer’s disease Metabolic correlates

Evaluation of Soybean Cultivars of Contrasting Cycles according to the Level of Investment in Fertilization

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American Journal of Plant Sciences 2017年第12期8卷 2977-2994页

作者： Emerson Borghi Eduardo de Paula Simao álvaro Vilela de Resende Joao Carlos Cardoso Galvao Sebastiao pedro da Silva neto André Ferreira Pereira Embrapa Maize and Sorghum SeteLagoasBrazil Department of Plant Science Federal University of VicosaVicosaBrazil EmbrapaCerrados PlanaltinaBrazil

The objective of the present study was to characterize the duration of the phenological stages, the agronomic characteristics and grain yield in soybean cultivars with contrasting cycles and indeterminate growth type, submitted to different fertilization investment environments under no-tillage system in the central region of Minas Gerais. The work was conducted under field conditions, in an experimental area of Embrapa Maize and Sorghum, in Sete Lagoas, MG, in the harvest of 2015/2016. Ten soybean cultivars with different relative maturity groups (RMG) were studied, representing almost all RMG materials currently sown in Minas Gerais, in two environments with different levels of fertilizer investment. The variables were submitted to analysis of joint variance, in order to verify the existence of interaction between cultivars and investment in fertilization environments. Fertilizer investment levels influence grain yield of soybean cultivars of contrasting cycles. The higher height of the soybean plants implies higher lodging and lower grain yield. This situation is aggravated by the greater investment in fertilization. The difference between the cycles of the cultivars is in the duration of the vegetative stages, being greater in the later cultivars.

关键词： Glycine max L.(Merrill) Growth Habit Relative Maturity Group

Economic Feasibility of Canola Production in the Region of Campos Gerais, Paraná, Brazil

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American Journal of Plant Sciences 2018年第5期9卷 958-965页

作者： Eriton Luiz Mainardes Luiz Cláudio Garcia pedro Henrique Weirich neto Carlos Hugo Rocha Thiago Inagaki Natali Maidl de Souza Guilherme pedrollo Mazer Jaime Alberti Gomes Ivan Cesar Furmann Moura éverson pedro Zeny State University of Ponta Grossa Campus Uvaranas Ponta Grossa Brasil

This study aimed to analyze the economic feasibility of canola production (Brassica napus var oleifera) for the region Campos Gerais-PR. We interviewed eight producers, and used information from four of them for economic analysis of agricultural crops in 2012, 2013 and 2014. The variables analyzed were: grain production cost, economical analysis (hurdle rate, net present value, internal rate of return, payback, lucratively index, profitability index and sensitivity analysis) and vegetable oil production costs. We compared the performance of canola, wheat (Triticum aestivum)—as the main crop in the autumn/winter—and soybean (Glycine max)—by liquidity in the world market. It was concluded that although the economic analysis indicates superior results of canola production compared to the wheat crop and vegetable oil production is more attractive financially than soybean, but the culture of canola is still insignificant in the region of Campos Gerais (PR). The producers interviewed pointed to limit the expansion of culture financing the limited farming, production technology in consolidation, the need for machine adjustments and canola be host of the white mold disease (Sclerotinia sclerotiorun).

关键词： Brassica napus Production Systems Profitability