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https://www.readbyqxmd.com/read/28944835/xanomeline-derivative-euk1001-attenuates-alzheimer-s-disease-pathology-in-a-triple-transgenic-mouse-model
#1
Ziyan Li, Kaili Jia, Yale Duan, Dong Wang, Zongli Zhou, Suzhen Dong
Agonists of M1 muscarinic acetylcholine receptors are promising therapeutic agents for the treatment of Alzheimer's disease (AD). An example of one of these agents is xanomeline, which has been a leading candidate, however induces various unwanted adverse effects. 3‑[3‑(3‑florophenyl‑2‑propyn‑1‑ylthio)‑1,2,5‑thiadiazol-4-yl]-1,2,5,6-tetrahydro‑1‑methylpyridine oxalate (EUK1001), a fluorinated derivative of xanomeline, has been demonstrated to attenuate AD‑like neurodegenerative pathology in presenilin‑deficient mice, which has no β‑amyloid (Aβ) pathology...
September 18, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28944565/novel-tetrahydroacridine-derivatives-with-iodobenzoic-acid-moiety-as-multifunctional-acetylcholinesterase-inhibitors
#2
Robert Skibiński, Kamila Czarnecka, Małgorzata Girek, Ireneusz Bilichowski, Nina Chufarova, Elżbieta Mikiciuk-Olasik, Paweł Szymański
New synthesized series of 9-amino-1,2,3,4-tetrahydroacridine derivatives with iodobenzoic acid moiety were studied for their inhibitory activity towards cholinesterase and against β-amyloid aggregation. All novel molecules 3a-3i interacted with both cholinesterases - acetylcholinesterase and butyrylcholinesterase, delivered nanomolar IC50 values. The structure-activity relationship showed that N-butyl moiety derivatives are stronger inhibitors towards AChE and BuChE than N-ethyl and N-propyl moieties compounds...
September 25, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28944295/towards-precision-medicine-in-alzheimer-s-disease-deciphering-genetic-data-to-establish-informative-biomarkers
#3
Ornit Chiba-Falek, Michael W Lutz
INTRODUCTION: Developing biomarker tools for identification of individuals at high-risk for late-onset Alzheimer's disease (LOAD) is important for prognosis and early treatment. This review focuses on genetic factors and their potential role for precision medicine in LOAD. AREAS COVERED: APOEe4 is the strongest genetic risk factor for non-Mendelian LOAD, and the APOE-linkage disequilibrium (LD) region has produced the most significant association signal in multi-center genome-wide-association-studies (GWAS)...
2017: Expert Review of Precision Medicine and Drug Development
https://www.readbyqxmd.com/read/28944218/diabetes-mitigates-the-role-of-memory-complaint-in-predicting-dementia-risk-results-from-the-prevention-of-alzheimer-s-disease-with-vitamin-e-and-selenium-study
#4
X Zhang, F A Schmitt, A M Caban-Holt, X Ding, R J Kryscio, E Abner
BACKGROUND: Subjective memory complaints (SMCs) are associated with increased risk of dementia in older adults, but the role of comorbidities in modifying this risk is unknown. OBJECTIVES: To assess whether comorbidities modify estimated dementia risk based on SMCs. DESIGN: The Prevention of Alzheimer's Disease with Vitamin E and Selenium Study (PREADVISE) was designed as an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized, multi-center prostate cancer prevention trial with sites in the Unites States, Puerto Rico, and Canada...
2017: Journal of Prevention of Alzheimer's Disease
https://www.readbyqxmd.com/read/28944107/ensemble-molecular-dynamics-of-a-protein-ligand-complex-residual-inhibitor-entropy-enhances-drug-potency-in-butyrylcholinesterase
#5
Eric J Sorin, Walter Alvarado, Samantha Cao, Amethyst Radcliffe, Phuc La, Yi An
Butyrylcholinesterase is a key enzyme that catalyzes the hydrolysis of the neurotransmitter acetylcholine and shows an increased activity in patients suffering from Alzheimer's disease (AD), making this enzyme a primary target in treating AD. Central to this problem, and to similar scenarios involving biomolecular recognition, is our understanding of the nature of the protein-ligand complex. The butyrylcholinesterase enzyme was studied via all-atom, explicit solvent, ensemble molecular dynamics simulations sans inhibitor and in the presence of three dialkyl phenyl phosphate inhibitors of known potency to a cumulative sampling of over 40 μs...
2017: Bioenergetics: Open Access
https://www.readbyqxmd.com/read/28943883/in-silico-analysis-of-binding-interaction-of-conantokins-with-nmda-receptors-for-potential-therapeutic-use-in-alzheimer-s-disease
#6
Maleeha Waqar, Sidra Batool
BACKGROUND: The N-methyl-D-aspartate (NMDA) receptors are glutamate receptors that play vital roles in central nervous system development and are involved in synaptic plasticity, which is an essential process for learning and memory. The subunit N-methyl D-aspartate receptor subtype 2B (NR2B) is the chief excitatory neurotransmitter receptor in the mammalian brain. Disturbances in the neurotransmission mediated by the NMDA receptor are caused by its overexposure to glutamate neurotransmitter and can be treated by its binding to an antagonist...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28943731/multi-source-multi-target-dictionary-learning-for-prediction-of-cognitive-decline
#7
Jie Zhang, Qingyang Li, Richard J Caselli, Paul M Thompson, Jieping Ye, Yalin Wang
Alzheimer's Disease (AD) is the most common type of dementia. Identifying correct biomarkers may determine pre-symptomatic AD subjects and enable early intervention. Recently, Multi-task sparse feature learning has been successfully applied to many computer vision and biomedical informatics researches. It aims to improve the generalization performance by exploiting the shared features among different tasks. However, most of the existing algorithms are formulated as a supervised learning scheme. Its drawback is with either insufficient feature numbers or missing label information...
June 2017: Information Processing in Medical Imaging: Proceedings of the ... Conference
https://www.readbyqxmd.com/read/28943632/differences-in-abca1-r219k-polymorphisms-and-serum-indexes-in-alzheimer-and-parkinson-diseases-in-northern-china
#8
Lagai Ya, Zuneng Lu
BACKGROUND ABCA1 R219K single-nucleotide polymorphisms (SNPs) was related to Alzheimer disease (AD) but not Parkinson disease (PD). Here, we analyzed the associations among ABCA1 R219K distribution, serum biomarkers, AD, and PD in a population in northern China. MATERIAL AND METHODS We used the Mini-Mental State Examination (MMSE) and the Hoehn and Yahr scale (H-Y) to evaluate AD and PD progression, separately. ABCA1 R219K was analyzed by matrix-assisted laser desorption ionization time of flight time mass spectrometry (MALDI-TOF-MS)...
September 25, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28943414/in-vivo-mri-assessment-of-the-human-locus-coeruleus-along-its-rostrocaudal-extent-in-young-and-older-adults
#9
Matthew J Betts, Arturo Cardenas-Blanco, Martin Kanowski, Frank Jessen, Emrah Düzel
The locus coeruleus (LC), a major origin of noradrenergic projections in the central nervous system (CNS), may serve a critical role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). As such, there is considerable interest to develop magnetic resonance imaging (MRI) techniques to assess the integrity of the LC in vivo. The high neuromelanin content of the LC serves as an endogenous contrast for MRI but existing protocols suffer from low spatial resolution along the rostrocaudal axis of the LC rendering it difficult to differentiate its integrity in caudal and rostral portions...
September 21, 2017: NeuroImage
https://www.readbyqxmd.com/read/28943355/boron-based-inhibitors-of-the-nlrp3-inflammasome
#10
Alex G Baldwin, Jack Rivers-Auty, Michael J D Daniels, Claire S White, Carl H Schwalbe, Tom Schilling, Halah Hammadi, Panichakorn Jaiyong, Nicholas G Spencer, Hazel England, Nadia M Luheshi, Manikandan Kadirvel, Catherine B Lawrence, Nancy J Rothwell, Michael K Harte, Richard A Bryce, Stuart M Allan, Claudia Eder, Sally Freeman, David Brough
NLRP3 is a receptor important for host responses to infection, yet is also known to contribute to devastating diseases such as Alzheimer's disease, diabetes, atherosclerosis, and others, making inhibitors for NLRP3 sought after. One of the inhibitors currently in use is 2-aminoethoxy diphenylborinate (2APB). Unfortunately, in addition to inhibiting NLRP3, 2APB also displays non-selective effects on cellular Ca(2+) homeostasis. Here, we use 2APB as a chemical scaffold to build a series of inhibitors, the NBC series, which inhibit the NLRP3 inflammasome in vitro and in vivo without affecting Ca(2+) homeostasis...
September 1, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28943286/polygenic-risk-score-of-sporadic-late-onset-alzheimer-s-disease-reveals-a-shared-architecture-with-the-familial-and-early-onset-forms
#11
Carlos Cruchaga, Jorge L Del-Aguila, Benjamin Saef, Kathleen Black, Maria Victoria Fernandez, John Budde, Laura Ibanez, Manav Kapoor, Giuseppe Tosto, Richard P Mayeux, David M Holtzman, Anne M Fagan, John C Morris, Randall J Bateman, Alison M Goate, Oscar Harari
OBJECTIVE: To determine whether the extent of overlap of the genetic architecture among the sporadic late-onset Alzheimer's Disease (sLOAD), familial late-onset AD (fLOAD), sporadic early-onset AD (sEOAD), and autosomal dominant early-onset AD (eADAD). METHODS: Polygenic risk scores (PRSs) were constructed using previously identified 21 genome-wide significant loci for LOAD risk. RESULTS: We found that there is an overlap in the genetic architecture among sEOAD, fLOAD, and sLOAD...
September 21, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28943206/kaolinite-in-pharmaceutics-and-biomedicine
#12
REVIEW
Mahmoud E Awad, Alberto López-Galindo, Massimo Setti, Mahmoud M El-Rahmany, César Viseras Iborra
Kaolinite Al2Si2O5(OH)4 is an abundant and inexpensive geomaterial regarded as one of the most common clay minerals in the earth's crust and the most widespread phase among the other kaolin polymorphs (halloysite, dickite and nacrite). Structurally, it is a hydrous aluminum phyllosilicate member belonging to the dioctahedral 1:1 kaolin mineral group. The particle size of the pseudohexagonal kaolinite platelets is normally <2μm (if compared to a human red blood cell of a typical diameter 6.2-8.2μm or to a virus particle of about 50nm diameter)...
September 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28943198/incidence-of-dementia-in-elderly-latin-americans-results-of-the-maracaibo-aging-study
#13
Gladys E Maestre, Luis J Mena, Jesus D Melgarejo, Daniel C Aguirre-Acevedo, Gloria Pino-Ramírez, Milady Urribarrí, Inara J Chacon, Carlos A Chávez, Luis Falque-Madrid, Ciro A Gaona, Joseph D Terwilliger, Joseph H Lee, Nikolaos Scarmeas
INTRODUCTION: There are few longitudinal studies of dementia in developing countries. We used longitudinal data from the Maracaibo Aging Study to accurately determine the age- and sex-specific incidence of dementia in elderly Latin Americans. METHODS: The Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) was used to diagnose dementia, which was classified as Alzheimer's disease, vascular dementia, or other. Age- and sex-specific incidence was estimated as the number of new cases of dementia divided by person-years (p-y) of follow-up...
September 21, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28943103/lower-vertebrate-and-invertebrate-models-of-alzheimer-s-disease-a-review
#14
REVIEW
Neha Sharma, Navneet Khurana, Arunachalam Muthuraman
Alzheimer's disease is a common neurodegenerative disorder which is characterized by the presence of beta- amyloid protein and neurofibrillary tangles (NFTs) in the brain. Till now, various higher vertebrate models have been in use to study the pathophysiology of this disease. But, these models possess some limitations like ethical restrictions, high cost, difficult maintenance of large quantity and lesser reproducibility. Besides, various lower chordate animals like Danio rerio, Drosophila melanogaster, Caenorhabditis elegans and Ciona intestinalis have been proved to be an important model for the in vivo determination of targets of drugs with least limitations...
September 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28942794/the-genetics-of-parkinson%C3%A2-disease
#15
Lina Mastrangelo
The 200years of research efforts on Parkinson disease (PD) form the basis of our understanding of the second most common neurodegenerative disorder after Alzheimer disease. This journey has been marked by the revolutionary discovery of a neurotransmitter replacement therapy that provides a longer and healthier life to patients. Since 1997, the advances in the genetics of PD have expanded our understanding of this neurodegenerative disorder and they are opening up new ways to search for disease-modifying therapies...
2017: Advances in Genetics
https://www.readbyqxmd.com/read/28942736/telephone-based-minnesota-cognitive-acuity-screen-predicts-time-to-institutionalization-and-homecare
#16
Seth A Margolis, George D Papandonatos, Geoffrey Tremont, Brian R Ott
BACKGROUND: We assessed the ability of a telephone-administered cognitive screening test - Minnesota Cognitive Acuity Screen (MCAS) - to predict time to assisted living/nursing home placement (i.e. institutionalization) and homecare/institutionalization in healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). METHODS: Participants (N = 146; HC = 37; MCI = 70; AD = 39) had baseline MCAS testing and were re-contacted over eight years for dates of starting homecare, institutionalization, and death...
September 25, 2017: International Psychogeriatrics
https://www.readbyqxmd.com/read/28942688/proteomic-studies-of-cerebrospinal-fluid-biomarkers-of-alzheimer-s-disease-an-update
#17
Erik Portelius, Gunnar Brinkmalm, Josef Pannee, Henrik Zetterberg, Kaj Blennow, Rahil Dahlén, Ann Westman-Brinkmalm, Johan Gobom
Alzheimer's disease (AD) is a neurodegenerative disease affecting the brain. Today there are three cerebrospinal fluid (CSF) biomarkers, amyloid-β consisting of 42 amino acids (Aβ42), total-tau (t-tau) and phosphorylated-tau (p-tau), which combined have sensitivity and specificity figures around 80%. However, pathological studies have shown that comorbidity is a common feature in AD and that the three currently used CSF biomarkers do not optimally reflect the activity of the disease process. Thus, additional markers are needed...
September 25, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28942474/svct2-expression-and-function-in-reactive-astrocytes-is-a-common-event-in-different-brain-pathologies
#18
Katterine Salazar, Fernando Martínez, Margarita Pérez-Martín, Manuel Cifuentes, Laura Trigueros, Luciano Ferrada, Francisca Espinoza, Natalia Saldivia, Romina Bertinat, Katherine Forman, María José Oviedo, Antonio J López-Gambero, Christian Bonansco, Ernesto R Bongarzone, Francisco Nualart
Ascorbic acid (AA), the reduced form of vitamin C, acts as a neuroprotector by eliminating free radicals in the brain. Sodium/vitamin C co-transporter isoform 2 (SVCT2) mediates uptake of AA by neurons. It has been reported that SVCT2 mRNA is induced in astrocytes under ischemic damage, suggesting that its expression is enhanced in pathological conditions. However, it remains to be established if SVCT expression is altered in the presence of reactive astrogliosis generated by different brain pathologies. In the present work, we demonstrate that SVCT2 expression is increased in astrocytes present at sites of neuroinflammation induced by intracerebroventricular injection of a GFP-adenovirus or the microbial enzyme, neuraminidase...
September 23, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28941799/regulatory-effects-of-simvastatin-and-apoj-on-app-processing-and-amyloid-%C3%AE-clearance-in-blood-brain-barrier-endothelial-cells
#19
Martina Zandl-Lang, Elham Fanaee-Danesh, Yidan Sun, Igor Čančar, Chaitanya Chakravarthi Gali, Alexandra Kober, Nicole M Albrecher, Carmen Tam-Amersdorfer, Anika Stracke, Steffen Storck, Ahmed Saeed, Jasminka Stefulj, Claus Pietrzik, Mark R Wilson, Ingemar Björkhem, Ute Panzenboeck
Amyloid-β peptides (Aβ) accumulate in cerebral capillaries indicating a central role of the blood-brain barrier (BBB) in the pathogenesis of Alzheimer's disease (AD). Although a relationship between apolipoprotein-, cholesterol- and Aβ metabolism is evident, the interconnecting mechanisms operating in brain capillary endothelial cells (BCEC) are poorly understood. ApoJ (clusterin) is present in HDL that regulates cholesterol metabolism which is disturbed in AD. ApoJ levels are increased in AD brains and in plasma of cerebral amyloid angiopathy (CAA) patients...
September 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28941755/the-diagnostic-value-of-fdg-and-amyloid-pet-in-alzheimer-s-disease-a-systematic-review
#20
REVIEW
Louise Rice, Sotirios Bisdas
PURPOSE: By 2050 it is projected that 115 million people worldwide will have Alzheimer's Disease (AD) [1]. Recent attempts have been made to redefine the diagnostic criteria of AD to include markers of neurodegeneration - measurable by FDG-PET - and markers of amyloid accumulation - measurable by amyloid-PET. MATERIALS AND METHODS: A systematic review of the literature was performed to examine the current diagnostic use of amyloid and FDG PET. MEDLINE and EMBASE databases and the Cochrane Database were searched for relevant papers RESULTS AND DISCUSSION: This search resulted in twenty-nine papers on amyloid imaging, twenty-three papers on FDG-PET and eight papers which utilized both techniques...
September 2017: European Journal of Radiology
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