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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

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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

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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

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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

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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

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Interactions between maternal parity and feed additives drive the composition of pig gut microbiomes in the post‑weaning period

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1241-1257页

作者： Kayla Law Eduardo rosa Medina Garcia Chad Hastad Deborah Murray pedro E.Urriola Andres Gomez Department of Animal Science University of Minnesota1364 Eckles AvenueSaint PaulMN 55108USA New Fashion Pork 164 Industrial ParkwayJacksonMN 56143USA

Background Nursery pigs undergo stressors in the post-weaning period that result in production and welfare *** challenges disproportionately impact the offspring of primiparous sows compared to those of mul-tiparous *** is known regarding potential interactions between parity and feed additives in the post-weaning period and their effects on nursery pig ***,the objective of this study was to investigate the effects of maternal parity on sow and offspring microbiomes and the influence of sow parity on pig fecal microbi-ome and performance in response to a prebiotic *** weaning,piglets were allotted into three treat-ment groups:a standard nursery diet including pharmacological doses of Zn and Cu(Con),a group fed a commercial prebiotic only(Preb)based on an Aspergillus oryzae fermentation extract,and a group fed the same prebiotic plus Zn and Cu(Preb+ZnCu).Results Although there were no differences in vaginal microbiome composition between primiparous and mul-tiparous sows,fecal microbiome composition was different(R^(2)=0.02,P=0.03).The fecal microbiomes of primiparous offspring displayed significantly higher bacterial diversity compared to multiparous offspring at d 0 and d 21 post-weaning(P<0.01),with differences in community composition observed at d 21(R^(2)=0.03,P=0.04).When analyzing the effects of maternal parity within each treatment,only the Preb diet triggered significant microbiome distinc-tions between primiparous and multiparous offspring(d 21:R^(2)=0.13,P=0.01;d 42:R^(2)=0.19,P=0.001).Composi-tional differences in pig fecal microbiomes between treatments were observed only at d 21(R^(2)=0.12,P=0.001).Pigs in the Con group gained significantly more weight throughout the nursery period when compared to those in the Preb+ZnCu *** Nursery pig gut microbiome composition was influenced by supplementation with an Aspergillus oryzae fermentation extract,with varying effects on performance

关键词： Aspergillus prebiotic Copper Feed additives Maternal Nursery pig microbiome Parity Swine microbiome Trace minerals Zinc

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Perspectives on a collaborative Canada-China research program on diagnostic biomarkers for pre-dementia stages of Alzheimer’s disease

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Journal of Translational Neuroscience 2017年第3期2卷 1-6页

作者： Serge Gauthier Jianping Jia Sylvie Belleville Simon Cloutier Dessa Sadovnick Colleen Guimond Laura Robb Mario Masellis Guy A Rouleau Liyong Wu pedro rosa-neto McGill Center for Studies in Aging Douglas Mental Health Research Institute Montreal H4H IR3 Canada Innovation Center for Neurological Disorders Department of Neurology Xuanwu Hospital Capital Medical University Beijing 100053 China Beijing Key Laboratory of Geriatric Cognitive Disorders Beijing 100053 China Clinical Center for Neurodegenerative Disease and Memory Impairment Capital Medical University Beijing 100053 China Center of Alzheimer's Disease Beijing Institute for Brain Disorders Beijing 100053 China Key Laboratory of Neurodegenerative Diseases Ministry of Education Beijing 100053 China National Clinical Research Center for Geriatric Disorders Beijing 100053 China Institut Universitaire de Gériatrie de Montréal Montréal H3W IW5 Canada Department of Medical Genetics University of British Columbia Vancouver V6T IZ4 Canada Division of Neurology Department of Medical Genetics University of British Columbia Vancouver V6T IZ4 Canada Division of Neurology/Department of Medicine Sunnybrook Health Sciences Centre University of Toronto Toronto M5S 3H7 Canada Hurvitz Brain Sciences Research Program Sunnybrook Research Institute Toronto M4N 3M5 Canada Montreal Neurological Institute Montréal H3A 2B4 Canada Department of Neurology Xuanwu Hospital Capital Medical University Beijing 100053 China

As biomarkers are important in the early diagnosis ofAlzheimer’s disease （AD）, the frst collab-orative work of recruiting early-onset familial AD （EO-FAD） families in Canada and China was initiated in 2012. The registration networks have collected hundreds of pedigrees, for which genetic screening, neuropsycholog-ical tests and amyloid and tau imaging was used to study diagnostic biomarkers for preclinical and mild cognitive impairment （MCI） stages of AD. Besides identifying ped-igrees with novel mutations in presenilins （PSENs）/amy-loid precursor protein （APP）, the program has benefted training of Chinese research fellows, AD clinical trials forprevention,the ethical concernsfor clinical fndings, and other collaborative projects with Chinese investiga-tors. Further research of the collaborative program may facilitate the testing and clinical use of novel treatments for EOFAD and late onset AD and contribute to dementia prevention strategies in Canada and China.

关键词： registration network early-onset fa-milial Alzheimer’s disease (EOFAD) mutation neuro-psychological testing

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Employing electrochemically derived pH gradients for Lab-on-PCB protein preconcentration devices

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Microsystems & Nanoengineering 2024年第1期10卷 79-87页

作者： Grace Maxted pedro Estrela Despina Moschou Department of Electronic and Electrical Engineering University of BathBath BA27AYUK Centre for Bioengineering and Biomedical Technologies(CBio) University of BathBath BA27AYUK

Protein preconcentration is an essential sample preparation step for analysis in which the targeted proteins exist in low concentrations,such as bodily fluids,water,or ***,very few practical implementations of miniaturized protein preconcentration devices have been demonstrated in practice,and even fewer have been integrated with other microanalytical *** approaches rely heavily on additional chemicals and reagents and introduce complexity to the overall *** this paper,we propose a novel miniaturized isoelectric focusing-based protein preconcentration screening device based on electrochemically derived pH gradients rather than existing chemical reagent *** this way,we reduce the need for additional chemical reagents to zero while enabling device incorporation in a seamlessly integrated full protein analysis microsystem via Lab-on-PCB *** apply our previously presented Lab-on-PCB approach to quantitatively control the pH of a solution in the vicinity of planar electrodes using electrochemical acid generation through redox-active self-assembled *** presented device comprises a printed circuit board with an array of gold electrodes that were functionalized with 4-aminothiophenol;this formed a self-assembled monolayer that was electropolymerized to improve its electrochemical *** preconcentration was performed in two *** first was open and needed the use of a holder to suspend a well of fluid above the electrodes;the second used microfluidic channels to enclose small volumes of *** here are the resulting data for protein preconcentration in both these forms,with a quantitative concentration factor shown for the open form and qualitative proof shown for the microfluidic.

关键词： electrochemical proof qualitative

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Conformational dynamics as an intrinsic determinant of prion protein misfolding and neurotoxicity

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Neural Regeneration Research 2024年第10期19卷 2095-2096页

作者： Alessandro Cembran pedro Fernandez-Funez Department of Chemistry and Biochemistry University of Minnesota DuluthDuluthMNUSA Department of Biomedical Sciences University of Minnesota Medical SchoolDuluth CampusDuluthMNUSA

The prion protein(PrP) is the key molecular and pathological mediator of prion diseases,a heterogeneous group of brain disorders with fatal *** diseases are rare but deserve special attention because of their unique f... 详细信息

关键词： folding intrinsic dynamics

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Effect of the Coulomb and dielectric forces on the onset of Rayleigh-Bénard convection

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Acta Mechanica Sinica 2024年第6期40卷 64-77页

作者： Zhonglin Du pedro A.Vázquez Jian Wu School of Energy Science and Engineering Harbin Institute of TechnologyHarbin150001China Heilongjiang Key Laboratory of Micro-and Nano-scale Fluid Flow and Heat Transfer Harbin150001China Departamento de Física Aplicada III ETSIIUniversidad de SevillaSevilla41092Spain

In this paper,the effect of Coulomb and dielectric forces on the onset of Rayleigh-Bénard convection(RBC)in a dielectric liquid layer contained between two parallel electrode plates has been numerically *** different operating conditions have been considered in electrohydrodynamic(EHD)conduction:ohmic and saturation,and variations in the physical properties of the dielectric fluid with *** electric equations and the state equations based on the Boussinesq approximation are integrated in the framework of OpenFOAM buoyantBoussinesqPimpleFoam *** results show that in the ohmic regime,the combined effect of Coulomb and dielectric forces promotes the onset of RBC flow,while in the saturation state,the inhibition of RBC flow by Coulomb force is more *** value of the critical Rayleigh number Ra decreases with increasing electric Reynolds number ReE in the ohmic regime,whereas in the saturation state,the critical Ra increases with increasing *** the saturation regime,the flow field always has a steady flow in the range of parameters ***,the onset of the RBC flow promoted by the dielectric force is more pronounced in the ohmic *** to the presence of the dielectric force,the flow field exhibits periodic oscillatory flow at low electric Reynolds numbers for the range of parameters considered.

关键词： EHD conduction Dielectric force Rayleigh-Bénard convection OpenFOAM

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