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https://www.readbyqxmd.com/read/28544981/synthesis-and-in%C3%A2-vitro-evaluation-of-new-fluorinated-quinoline-derivatives-with-high-affinity-for-pde5-towards-the-development-of-new-pet-neuroimaging-probes
#1
Jianrong Liu, Aurélie Maisonial-Besset, Barbara Wenzel, Damien Canitrot, Ariane Baufond, Jean-Michel Chezal, Peter Brust, Emmanuel Moreau
The increasing incidence of Alzheimer's disease (AD) worldwide is a major public health problem. Current treatments provide only palliative solutions with significant side effects. Therefore, new efficient treatment options and novel early diagnosis tools are urgently needed. Recently, strong pre-clinical evidences suggested that phosphodiesterase 5 (PDE5) may be clinically relevant both as biomarker and drug-target in AD. In this study, we intended to develop a new radiofluorinated tracer for the visualisation of PDE5 in brain using PET imaging...
April 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28543731/neuroimaging-biomarkers-and-impaired-olfaction-in-cognitively-normal-individuals
#2
Maria Vassilaki, Teresa J Christianson, Michelle M Mielke, Yonas E Geda, Walter K Kremers, Mary M Machulda, David S Knopman, Ronald C Petersen, Val J Lowe, Clifford R Jack, Rosebud O Roberts
OBJECTIVE: There is a need for inexpensive non-invasive tests to identify older healthy persons at risk for Alzheimer's disease (AD) for enrollment in AD prevention trials. Our objective was to examine whether abnormalities in neuroimaging measures of amyloid and neurodegeneration are correlated with odor identification (OI) in the population-based Mayo Clinic Study of Aging (MCSA). METHODS: Cognitively normal (CN) participants had olfactory function assessed using the Brief Smell Identification Test (B-SIT), underwent magnetic resonance imaging (MRI; n=829) to assess a composite Alzheimer's disease (AD) signature cortical thickness and hippocampal volume (HVa), and, (11) C-Pittsburgh compound B ((11) C-PiB; n=306) and (18) fluorodeoxyglucose ((18) F-FDG; n=305) positron emission tomography (PET) scanning to assess amyloid accumulation and brain hypometabolism, respectively...
May 22, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28539126/knowledge-driven-binning-approach-for-rare-variant-association-analysis-application-to-neuroimaging-biomarkers-in-alzheimer-s-disease
#3
Dokyoon Kim, Anna O Basile, Lisa Bang, Emrin Horgusluoglu, Seunggeun Lee, Marylyn D Ritchie, Andrew J Saykin, Kwangsik Nho
BACKGROUND: Rapid advancement of next generation sequencing technologies such as whole genome sequencing (WGS) has facilitated the search for genetic factors that influence disease risk in the field of human genetics. To identify rare variants associated with human diseases or traits, an efficient genome-wide binning approach is needed. In this study we developed a novel biological knowledge-based binning approach for rare-variant association analysis and then applied the approach to structural neuroimaging endophenotypes related to late-onset Alzheimer's disease (LOAD)...
May 18, 2017: BMC Medical Informatics and Decision Making
https://www.readbyqxmd.com/read/28538088/effects-of-the-insulin-sensitizer-metformin-in-alzheimer-disease-pilot-data-from-a-randomized-placebo-controlled-crossover-study
#4
Aaron M Koenig, Dawn Mechanic-Hamilton, Sharon X Xie, Martha F Combs, Anne R Cappola, Long Xie, John A Detre, David A Wolk, Steven E Arnold
Epidemiological studies have identified a robust association between type II diabetes mellitus and Alzheimer disease (AD), and neurobiological studies have suggested the presence of central nervous system insulin resistance in individuals with AD. Given this association, we hypothesized that the central nervous system-penetrant insulin-sensitizing medication metformin would be beneficial as a disease-modifying and/or symptomatic therapy for AD, and conducted a placebo-controlled crossover study of its effects on cerebrospinal fluid (CSF), neuroimaging, and cognitive biomarkers...
April 2017: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/28538087/total-brain-and-hippocampal-volumes-and-cognition-in-older-american-indians-the-strong-heart-study
#5
Brenna Cholerton, Adam Omidpanah, Tara M Madhyastha, Thomas J Grabowski, Astrid M Suchy-Dicey, Dean K Shibata, Lonnie A Nelson, Steven P Verney, Barbara V Howard, William T Longstreth, Thomas J Montine, Dedra Buchwald
BACKGROUND: Estimates of hippocampal volume by magnetic resonance imaging have clinical and cognitive correlations and can assist in early Alzheimer disease diagnosis. However, little is known about the relationship between global or regional brain volumes and cognitive test performance in American Indians. MATERIALS AND METHODS: American Indian participants (N=698; median age, 72 y) recruited for the Cerebrovascular Disease and its Consequences in American Indians study, an ancillary study of the Strong Heart Study cohort, were enrolled...
April 2017: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/28535786/biochemical-markers-in-vascular-cognitive-impairment-associated-with-subcortical-small-vessel-disease-a-consensus-report
#6
A Wallin, E Kapaki, M Boban, S Engelborghs, D M Hermann, B Huisa, M Jonsson, M G Kramberger, L Lossi, B Malojcic, S Mehrabian, A Merighi, E B Mukaetova-Ladinska, G P Paraskevas, B O Popescu, R Ravid, L Traykov, G Tsivgoulis, G Weinstein, A Korczyn, M Bjerke, G Rosenberg
BACKGROUND: Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data...
May 23, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28534796/predicting-progression-from-mild-cognitive-impairment-to-alzheimer-s-disease-using-autoregressive-modelling-of-longitudinal-and-multimodal-biomarkers
#7
Sidra Minhas, Aasia Khanum, Farhan Riaz, Shoab Khan, Atif Alvi
Mild Cognitive Impairment is a preclinical stage of Alzheimer's disease (AD). For effective treatment of AD, it is important to identify MCI patients who are at a high risk of developing AD over the course of time. İn this study, autoregressive modelling of multiple heterogeneous predictors of Alzheimer's dısease is performed to capture their evolution over time. The models are trained using three different arrangements of longitudinal data. These models are then used to estimate future biomarker readings of individual test subjects...
May 16, 2017: IEEE Journal of Biomedical and Health Informatics
https://www.readbyqxmd.com/read/28533191/mir-34a-knockout-attenuates-cognitive-deficits-in-app-ps1-mice-through-inhibition-of-the-amyloidogenic-processing-of-app
#8
Chongdong Jian, Mengru Lu, Zhao Zhang, Long Liu, Xianfeng Li, Fang Huang, Ning Xu, Lina Qin, Qian Zhang, Donghua Zou
The noncoding miRNA-34a (miR-34a) is involved in Alzheimer's disease (AD) pathologenesis and shows potential for application as a biomarker for early diagnosis and intervention. Here, we established miR-34a knockout mice in an APP/PS1 background (APP/PS1-miR-34a KO mice) by crossbreeding miR-34a(-/-) mice with APP/PS1 mice. We then investigated cognitive impairment and related pathologies. The results showed that the level of miR-34a was increased at about 6months in APP/PS1 mice, consistent with the increase in amyloid β (Aβ), and cognitive function was significantly improved in mice when miR-34a was knocked out in 9-month-old and 12-month-old mice, indicating that miR-34a is a potential candidate for determining the progression of AD...
May 19, 2017: Life Sciences
https://www.readbyqxmd.com/read/28527630/diagnostic-accuracy-of-csf-neurofilament-light-chain-protein-in-the-biomarker-guided-classification-system-for-alzheimer-s-disease
#9
Simone Lista, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Bruno Dubois, Roberto Floris, Francesco Garaci, Harald Hampel
We assessed the diagnostic accuracy of cerebrospinal fluid (CSF) neurofilament light chain (NFL) protein in the classification of patients with Alzheimer's disease (AD) and cognitively healthy control individuals (HCs) and patients with frontotemporal dementia (FTD) as comparisons. Particularly, we tested the performance of CSF NFL concentration in differentiating patient groups stratified by fluid biomarker profiles, independently of the severity of cognitive impairment (mild cognitive impairment (MCI) and AD dementia individuals), using a biomarker-guided descriptive classification system for AD...
May 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28527217/protein-phosphorylation-is-a-key-mechanism-in-alzheimer-s-disease
#10
Joana Oliveira, Márcio Costa, Maria Soares Cachide de Almeida, Odete A B da Cruz E Silva, Ana Gabriela Henriques
Altered protein phosphorylation states of several proteins are closely associated with Alzheimer's disease (AD). Among these are the amyloid-β precursor protein (AβPP) and the tau protein. In fact, altered protein phosphorylation states already provide strong biomarkers for AD diagnosis, as is the case with hyperphosphorylated tau. It follows that modulating signaling cascades provides an attractive avenue for exploring novel therapeutic strategies. This review focuses on some of the major protein kinases and protein phosphatases relevant to AD...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28527215/diagnostic-and-prognostic-value-of%C3%A2-the%C3%A2-combination-of-two-measures-of%C3%A2-verbal-memory-in-mild-cognitive-impairment-due%C3%A2-to-alzheimer-s-disease
#11
Isabel Sala, Ignacio Illán-Gala, Daniel Alcolea, Ma Belén Sánchez-Saudinós, Sergio Andrés Salgado, Estrella Morenas-Rodríguez, Andrea Subirana, Laura Videla, Jordi Clarimón, María Carmona-Iragui, Roser Ribosa-Nogué, Rafael Blesa, Juan Fortea, Alberto Lleó
BACKGROUND: Episodic memory impairment is the core feature of typical Alzheimer's disease. OBJECTIVE: To evaluate the performance of two commonly used verbal memory tests to detect mild cognitive impairment due to Alzheimer's disease (MCI-AD) and to predict progression to Alzheimer's disease dementia (AD-d). METHODS: Prospective study of MCI patients in a tertiary memory disorder unit. Patients underwent an extensive neuropsychological battery including two tests of declarative verbal memory: The Free and Cued Selective Reminding Test (FCSRT) and the word list learning task from the Consortium to Establish a Registry for Alzheimer's disease (CERAD-WL)...
May 13, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28527210/cerebrospinal-fluid-biomarkers-and-clinical-progression-in-patients-with-subjective-cognitive-decline-and-mild-cognitive-impairment
#12
Steffen Wolfsgruber, Alexandra Polcher, Alexander Koppara, Luca Kleineidam, Lutz Frölich, Oliver Peters, Michael Hüll, Eckart Rüther, Jens Wiltfang, Wolfgang Maier, Johannes Kornhuber, Piotr Lewczuk, Frank Jessen, Michael Wagner
BACKGROUND: There is very limited data on the prevalence of abnormal cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and their predictive value for clinical progression in memory clinic patients with subjective cognitive decline (SCD). OBJECTIVE: To assess the frequency of abnormal CSF biomarkers of AD and their predictive value for clinical progression in memory clinic patients with SCD in comparison to patients with mild cognitive impairment (MCI) from the same cohort...
May 13, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28523532/progressive-pathological-changes-in-neurochemical-profile-of-the-hippocampus-and-early-changes-in-the-olfactory-bulbs-of-tau-transgenic-mice-rtg4510
#13
Jieun Kim, In-Young Choi, Karen E Duff, Phil Lee
Tauopathies such as Alzheimer's disease and frontotemporal lobe degeneration (FTLD-tau) dementia, characterized by pathologic aggregation of the microtubule-associated tau protein and formation of neurofibrillary tangles, have been linked to neurodegeneration and cognitive decline. The early detection of cerebral abnormalities and the identification of biological contributors to the continuous pathologic processes of neurodegeneration in tauopathies critically hinge on sensitive and reliable measures of biomarkers in the living brain...
May 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28523372/dietary-eicosapentaenoic-acid-normalizes-hippocampal-omega-3-and-6-polyunsaturated-fatty-acid-profile-attenuates-glial-activation-and-regulates-bdnf-function-in-a-rodent-model-of-neuroinflammation-induced-by-central-interleukin-1%C3%AE-administration
#14
Yilong Dong, Min Xu, Allan V Kalueff, Cai Song
PURPOSE: Interleukin (IL)-1β can activate glial cells to trigger neuroinflammation and neurodegeneration. Lower omega (n)-3 polyunsaturated fatty acids (PUFAs) and lower n-3/n-6 PUFA ratios occur in the brain of patients with Alzheimer's disease (AD). We have previously reported that an n-3 PUFA, eicosapentaenoic acid (EPA), can improve memory and attenuate neurodegeneration-like changes in animal models of AD. However, whether and how EPA modulates glial cell activity and functions remains unclear...
May 18, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28521765/inhibition-of-o-glcnacase-leads-to-elevation-of-o-glcnac-tau-and-reduction-of-tauopathy-and-cerebrospinal-fluid-tau-in-rtg4510-mice
#15
Nicholas B Hastings, Xiaohai Wang, Lixin Song, Brent D Butts, Diane Grotz, Richard Hargreaves, J Fred Hess, Kwok-Lam Karen Hong, Cathy Ruey-Ruey Huang, Lynn Hyde, Maureen Laverty, Julie Lee, Diane Levitan, Sherry X Lu, Maureen Maguire, Veeravan Mahadomrongkul, Ernest J McEachern, Xuesong Ouyang, Thomas W Rosahl, Harold Selnick, Michaela Stanton, Giuseppe Terracina, David J Vocadlo, Ganfeng Wang, Joseph L Duffy, Eric M Parker, Lili Zhang
BACKGROUND: Hyperphosphorylation of microtubule-associated protein tau is a distinct feature of neurofibrillary tangles (NFTs) that are the hallmark of neurodegenerative tauopathies. O-GlcNAcylation is a lesser known post-translational modification of tau that involves the addition of N-acetylglucosamine onto serine and threonine residues. Inhibition of O-GlcNAcase (OGA), the enzyme responsible for the removal of O-GlcNAc modification, has been shown to reduce tau pathology in several transgenic models...
May 18, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28520803/multiple-modality-biomarker-prediction-of-cognitive-impairment-in-prospectively-followed-de-novo-parkinson-disease
#16
Chelsea Caspell-Garcia, Tanya Simuni, Duygu Tosun-Turgut, I-Wei Wu, Yu Zhang, Mike Nalls, Andrew Singleton, Leslie A Shaw, Ju-Hee Kang, John Q Trojanowski, Andrew Siderowf, Christopher Coffey, Shirley Lasch, Dag Aarsland, David Burn, Lana M Chahine, Alberto J Espay, Eric D Foster, Keith A Hawkins, Irene Litvan, Irene Richard, Daniel Weintraub
OBJECTIVES: To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments. METHODS: We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition...
2017: PloS One
https://www.readbyqxmd.com/read/28520598/imaging-plus-x-multimodal-models-of-neurodegenerative-disease
#17
Neil P Oxtoby, Daniel C Alexander
PURPOSE OF REVIEW: This article argues that the time is approaching for data-driven disease modelling to take centre stage in the study and management of neurodegenerative disease. The snowstorm of data now available to the clinician defies qualitative evaluation; the heterogeneity of data types complicates integration through traditional statistical methods; and the large datasets becoming available remain far from the big-data sizes necessary for fully data-driven machine-learning approaches...
May 16, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28518113/enhanced-sample-multiplexing-of-tissues-using-combined-precursor-isotopic-labeling-and-isobaric-tagging-cpilot
#18
Christina D King, Joseph D Dudenhoeffer, Liqing Gu, Adam R Evans, Renã A S Robinson
There is an increasing demand to analyze many biological samples for disease understanding and biomarker discovery. Quantitative proteomics strategies that allow simultaneous measurement of multiple samples have become widespread and greatly reduce experimental costs and times. Our laboratory developed a technique called combined precursor isotopic labeling and isobaric tagging (cPILOT), which enhances sample multiplexing of traditional isotopic labeling or isobaric tagging approaches. Global cPILOT can be applied to samples originating from cells, tissues, bodily fluids, or whole organisms and gives information on relative protein abundances across different sample conditions...
May 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28515688/insulin-resistance-as-a-link-between-amyloid-beta-and-tau-pathologies-in-alzheimer-s-disease
#19
Roger J Mullins, Thomas C Diehl, Chee W Chia, Dimitrios Kapogiannis
Current hypotheses and theories regarding the pathogenesis of Alzheimer's disease (AD) heavily implicate brain insulin resistance (IR) as a key factor. Despite the many well-validated metrics for systemic IR, the absence of biomarkers for brain-specific IR represents a translational gap that has hindered its study in living humans. In our lab, we have been working to develop biomarkers that reflect the common mechanisms of brain IR and AD that may be used to follow their engagement by experimental treatments...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28515555/quantitative-balance-and-gait-measurement-in-patients-with-frontotemporal-dementia-and-alzheimer-diseases-a-pilot-study
#20
Selva Ganapathy Velayutham, Sadanandavalli Retnaswami Chandra, Srikala Bharath, Ravi Girikamatha Shankar
INTRODUCTION: Alzhiemers disease and Frontotemporal dementia are common neurodegenerative dementias with a wide prevalence. Falls are a common cause of morbidity in these patients. Identifying subclinical involvement of these parameters might serve as a tool in differential analysis of these distinct parameters involved in these conditions and also help in planning preventive strategies to prevent falls. PATIENTS AND METHODS: Eight patients in age and gender matched patients in each group were compared with normal controls...
March 2017: Indian Journal of Psychological Medicine
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