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https://www.readbyqxmd.com/read/27923632/puerarin-suppression-of-a%C3%AE-1-42-induced-primary-cortical-neuron-death-is-largely-dependent-on-er%C3%AE
#1
Li Li, Zuguang Xue, Lei Chen, Xueyu Chen, Heshuang Wang, Xiaobo Wang
Recent study has suggested that estrogen replacement therapy (ERT) can decrease the risk of the development of Alzheimer's disease (AD), and phytoestrogen has been proposed as a potential alternative to ERT. In this study, we investigated the protective function of puerarin (a phytoestrogen isolated from puerarin lobate) against amyloid beta (Aβ1-42)-induced toxicity in cortical neurons and established the connection between such a protection and estrogen receptor (ER) activation. Puerarin suppressed Aβ1-42-induced cortical neuron death in a concentration-dependent manner...
December 3, 2016: Brain Research
https://www.readbyqxmd.com/read/27917876/soluble-amyloid-beta-aggregates-from-human-alzheimer-s-disease-brains
#2
Thomas J Esparza, Norelle C Wildburger, Hao Jiang, Mihika Gangolli, Nigel J Cairns, Randall J Bateman, David L Brody
Soluble amyloid-beta (Aβ) aggregates likely contribute substantially to the dementia that characterizes Alzheimer's disease. However, despite intensive study of in vitro preparations and animal models, little is known about the characteristics of soluble Aβ aggregates in the human Alzheimer's disease brain. Here we present a new method for extracting soluble Aβ aggregates from human brains, separating them from insoluble aggregates and Aβ monomers using differential ultracentrifugation, and purifying them >6000 fold by dual antibody immunoprecipitation...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917270/effect-of-creatine-supplementation-on-cognitive-performance-and-apoptosis-in-a-rat-model-of-amyloid-beta-induced-alzheimer-s-disease
#3
Malek Alimohammadi-Kamalabadi, Mohammadreza Eshraghian, Mohammad-Reza Zarindast, Abbas Aliaghaei, Hamideh Pishva
OBJECTIVES: Neuroprotective effect of creatine (Cr) against β-amyloid (Aβ) is reported in an in vitro study. This study investigated the effect of Cr supplementation on β-amyloid toxicity in vivo. MATERIALS AND METHODS: Thirty two, male Wistar rats were divided into 4 groups. During ten weeks of study, control group went through no surgical or dietary intervention. At the 4th week of study Sham group had a hippocampal normal saline injection, while Aβ and AβCr groups had an β-amyloid injection in the hippocampus...
November 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27915995/lack-of-p-glycoprotein-results-in-impairment-of-removal-of-beta-amyloid-and-increased-intraparenchymal-cerebral-amyloid-angiopathy-after-active-immunization-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#4
Sascha Brückmann, Anja Brenn, Markus Grube, Katharina Niedrig, Silva Holtfreter, Oliver von Bohlen Und Halbach, Martin Groschup, Markus Keller, Silke Vogelgesang
Immunization against beta-amyloid (Aβ) reduces cerebral Aβ deposits and improves cognitive capacities in transgenic mouse models, and thus has been considered a promising disease-modifying therapeutic approach for Alzheimer's disease (AD). Although clinical trials in AD patients have yielded evidence for clearance of parenchymal Aβ plaques, Aβ increases in blood vessels of treated patients. We hypothesize that an age-related decline in the mechanisms that clear Aβ from the brain might be at least in part responsible for the failure to purge and re-distribute Aβ...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27915236/alcohol-and-alzheimer-s-disease-does-alcohol-dependence-contribute-to-beta-amyloid-deposition-neuroinflammation-and-neurodegeneration-in-alzheimer-s-disease
#5
Ashwin Venkataraman, Nicola Kalk, Gavin Sewell, Craig W Ritchie, Anne Lingford-Hughes
AIMS: To investigate the underlying neurobiology between alcohol use, misuse and dependence and cognitive impairment, particularly Alzheimer's disease (AD). METHODS: Review of the literature using searches of Medline, Pubmed, EMBASE, PsycInfo, and meeting abstracts and presentations. RESULTS: The role of alcohol as a risk factor and contributor for cognitive decline associated with AD has received little attention. This is despite the high prevalence of alcohol use, the potential reversibility of a degree of cognitive impairment and the global burden of AD...
December 3, 2016: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
https://www.readbyqxmd.com/read/27914799/computational-approach-for-the-assessment-of-inhibitory-potency-against-beta-amyloid-aggregation
#6
Marek Bajda, Sławomir Filipek
Beta-amyloid (Aβ) plaques are one of the hallmarks of Alzheimer's disease. Their presence in the brain leads to neurodegeneration and memory decline. Therefore, search for new drugs able to decrease formation of such deposits is of great interest. Our previously developed multifunctional compounds inhibited transformation of monomers into fibrils. Herein, we describe the computational approach for the assessment of inhibitory activity against Aβ aggregation. The influence of novel inhibitors on amyloid Aβ17-42 was studied by employing of molecular docking and all-atom molecular dynamics simulations...
November 24, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27913965/plasma-amyloid-beta-levels-in-patients-with-different-types-of-cancer
#7
Wang-Sheng Jin, Xian-Le Bu, Yu-Hui Liu, Lin-Lin Shen, Zhen-Qian Zhuang, Shu-Sheng Jiao, Chi Zhu, Qing-Hua Wang, Hua-Dong Zhou, Tao Zhang, Yan-Jiang Wang
Several epidemiological investigations indicate that cancer survivors have a lower risk for Alzheimer's disease (AD) and vice versa. However, the associations between plasma amyloid-beta (Aβ) levels with cancer remain largely unknown. In this case-control study, 110 cancer patients, 70 AD patients, and 70 age- and gender-matched normal controls were recruited. The cancer types include esophagus cancer, colorectal cancer, hepatic cancer, and lung cancer, all of which were reported to be associated with a lower risk for AD...
December 3, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27913818/-amyloid-positron-emission-tomography-with-18-%C3%A2-f-florbetaben-in-the-diagnostic-workup-of-dementia-patients
#8
S Schönecker, C Prix, T Raiser, N Ackl, E Wlasich, G Stenglein-Krapf, E Mille, M Brendel, O Sabri, M Patt, H Barthel, P Bartenstein, J Levin, A Rominger, A Danek
BACKGROUND: To this day the definite diagnosis of Alzheimer's disease still relies on post-mortem histopathological detection of neurofibrillary tangles and beta-amyloid deposits. Amyloid positron emission tomography (PET) is a new diagnostic tool that enables the in vivo quantification of pathological beta-amyloid deposits. The aim of the current study was to evaluate to what extent (18)F-florbetaben-PET (FBB-PET) influences the diagnosis of patients with dementia. MATERIAL AND METHODS: Imaging with FBB-PET was performed on 33 patients from our outpatient department for cognitive neurology...
December 2, 2016: Der Nervenarzt
https://www.readbyqxmd.com/read/27911757/local-and-use-dependent-effects-of-%C3%AE-amyloid-oligomers-on-nmda-receptor-function-revealed-by-optical-quantal-analysis
#9
Brooke L Sinnen, Aaron B Bowen, Emily S Gibson, Matthew J Kennedy
: Beta amyloid (Aβ) triggers the elimination of excitatory synaptic connections in the CNS, an early manifestation of Alzheimer's disease. Oligomeric assemblies of Aβ peptide associate with excitatory synapses resulting in synapse elimination through a process that requires NMDA-type glutamate receptor activation. Whether Aβ affects synaptic NMDA receptor (NMDAR) function directly and acts locally at synapses to which it has bound and whether synaptic activity influences Aβ synaptic binding and synaptotoxicity have remained fundamental questions...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27911039/para-sulfonato-calix-n-arenes-inhibit-amyloid-beta-peptide-fibrillation-and-reduce-amyloid-cytotoxicity
#10
Ziyuan Wang, Shipeng Tao, Xiaoyan Dong, Yan Sun
Amyloid β-peptides (Aβ) fibrillation is a major hallmark of Alzheimer's disease (AD). Inhibition of Aβ fibrillation is thus considered as an effective strategy for AD prevention and treatment. Here we show that para-sulfonato-calix[n]arenes (SC[n]A, n=4, 6, 8), a class of amphiphilic calixarene derivatives, can bind to Aβ42 through nonspecific and multipoint hydrophobic interactions. Their binding leads to a pronounced delay in β-sheet adoption and formation of multiple secondary structures of the peptide, accompanied by changes at the level of the fibrillary architecture...
December 2, 2016: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/27909398/an-amyloid-like-pathological-conformation-of-tdp-43-is-stabilized-by-hypercooperative-hydrogen-bonds
#11
Miguel Mompeán, Marco Baralle, Emanuele Buratti, Douglas V Laurents
TDP-43 is an essential RNA-binding protein forming aggregates in almost all cases of sporadic amyotrophic lateral sclerosis (ALS) and many cases of frontotemporal lobar dementia (FTLD) and other neurodegenerative diseases. TDP-43 consists of a folded N-terminal domain with a singular structure, two RRM RNA-binding domains, and a long disordered C-terminal region which plays roles in functional RNA regulatory assemblies as well as pernicious aggregation. Evidence from pathological mutations and seeding experiments strongly suggest that TDP-43 aggregates are pathologically relevant through toxic gain-of-harmful-function and/or harmful loss-of-native-function mechanisms...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27908798/platelets-are-responsible-for-the-accumulation-of-%C3%AE-amyloid-in-blood-clots-inside-and-around-blood-vessels-in-mouse-brain-after-thrombosis
#12
Lilia Y Kucheryavykh, Josué Dávila-Rodríguez, David E Rivera-Aponte, Lidia V Zueva, A Valance Washington, Priscilla Sanabria, Mikhail Y Inyushin
INTRODUCTION: Platelets contain beta-amyloid precursor protein (APP) as well as Aβ peptide (Aβ) that can be released upon activation. During thrombosis, platelets are concentrated in clots and activated. METHODS: We used in vivo fluorescent analysis and electron microscopy in mice to determine to what degree platelets are concentrated in clots. We used immunostaining to visualize Aβ after photothrombosis in mouse brains. RESULTS: Both in vivo results and electron microscopy revealed that platelets were 300-500 times more concentrated in clots than in non-clotted blood...
November 28, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27908343/a%C3%AE-amyloid-pathology-affects-the-hearts-of-patients%C3%A2-with%C3%A2-alzheimer-s-disease-mind%C3%A2-the-heart
#13
Luca Troncone, Marco Luciani, Matthew Coggins, Elissa H Wilker, Cheng-Ying Ho, Kari Elise Codispoti, Matthew P Frosch, Rakez Kayed, Federica Del Monte
BACKGROUND: Individually, heart failure (HF) and Alzheimer's disease (AD) are severe threats to population health, and their potential coexistence is an alarming prospect. In addition to sharing analogous epidemiological and genetic profiles, biochemical characteristics, and common triggers, the authors recently recognized common molecular and pathological features between the 2 conditions. Whereas cognitive impairment has been linked to HF through perfusion defects, angiopathy, and inflammation, whether patients with AD present with myocardial dysfunction, and if the 2 conditions bear a common pathogenesis as neglected siblings are unknown...
December 6, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27906619/effects-of-4-pyridone-3-carboxamide-1%C3%AE-d-ribonucleoside-on-adenine-nucleotide-catabolism-in-the-aortic-wall-implications-for-atherosclerosis-in-apoe-ldlr-mice
#14
Magdalena Zabielska, Barbara Kutryb-Zajac, Paulina Żukowska, Ewa Slominska, Ryszard Smoleński
: 4-Pyridone-3-carboxamide-1-beta-D-ribonucleoside (4PYR) is an endogenously produced nucleoside that had been identified as a substrate for intracellular phosphorylation to form intracellular nucleotides. Previous studies demonstrated that 4PYR adversely affects metabolism of endothelial cells that is known risk factor for atherosclerosis. The purpose of this study was to evaluate effects of 4PYR on the progression of atherosclerosis and changes in extracellular nucleotides degradation on the surface of the vessel wall in the murine model...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906438/cholinesterase-inhibitors-and-non-steroidal-anti-inflammatory-drugs-as-alzheimer-s-disease-therapies-an-updated-umbrella-review-of-systematic-reviews-and-meta-analyses
#15
C-H Wang, L-S Wang, N Zhu
OBJECTIVE: Alzheimer's Disease (AD) is a major neurological disorder marked by an amyloid-beta plaque and neurofibrillary tau-tangle depositions in the brain. Cognitive dysfunction is the key manifestation of AD. In this study, we conducted an umbrella review of meta-analyses on the risk factors and therapeutics targeting cognitive impairment and AD. MATERIALS AND METHODS: We searched PubMed from January 2000-August, 2016, and screened systematic reviews and meta-analyses of studies that examined the effects of cholinesterase inhibitors in AD patients...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27904493/beta-2-adrenergic-receptor-activation-enhances-neurogenesis-in-alzheimer-s-disease-mice
#16
Gao-Shang Chai, Yang-Yang Wang, Amina Yasheng, Peng Zhao
Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer's disease. Enhancing adult hippocampal neurogenesis has been pursued as a potential therapeutic strategy for Alzheimer's disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer's disease...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27901073/thd-module-extractor-an-application-for-cen-module-extraction-and-interesting-gene-identification-for-alzheimer-s-disease
#17
Tulika Kakati, Hirak Kashyap, Dhruba K Bhattacharyya
There exist many tools and methods for construction of co-expression network from gene expression data and for extraction of densely connected gene modules. In this paper, a method is introduced to construct co-expression network and to extract co-expressed modules having high biological significance. The proposed method has been validated on several well known microarray datasets extracted from a diverse set of species, using statistical measures, such as p and q values. The modules obtained in these studies are found to be biologically significant based on Gene Ontology enrichment analysis, pathway analysis, and KEGG enrichment analysis...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895577/fus1-ko-mouse-as-a-model-of-oxidative-stress-mediated-sporadic-alzheimer-s-disease-circadian-disruption-and-long-term-spatial-and-olfactory-memory-impairments
#18
Guillermo Coronas-Samano, Keeley L Baker, Winston J T Tan, Alla V Ivanova, Justus V Verhagen
Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27895104/bin1-and-cd2ap-polarise-the-endocytic-generation-of-beta-amyloid
#19
Florent Ubelmann, Tatiana Burrinha, Laura Salavessa, Ricardo Gomes, Cláudio Ferreira, Nuno Moreno, Cláudia Guimas Almeida
The mechanisms driving pathological beta-amyloid (Aβ) generation in late-onset Alzheimer's disease (AD) are unclear. Two late-onset AD risk factors, Bin1 and CD2AP, are regulators of endocytic trafficking, but it is unclear how their endocytic function regulates Aβ generation in neurons. We identify a novel neuron-specific polarisation of Aβ generation controlled by Bin1 and CD2AP We discover that Bin1 and CD2AP control Aβ generation in axonal and dendritic early endosomes, respectively. Both Bin1 loss of function and CD2AP loss of function raise Aβ generation by increasing APP and BACE1 convergence in early endosomes, however via distinct sorting events...
November 28, 2016: EMBO Reports
https://www.readbyqxmd.com/read/27894893/the-blood-brain-barrier-in-alzheimer-s-disease
#20
REVIEW
A Chakraborty, N M de Wit, W M van der Flier, H E de Vries
Alzheimer's disease (AD) is the most common form of dementia, affecting millions of people worldwide. One of the prominent causative factors of AD pathogenesis is cerebral vascular dysfunction, which results in diminished cerebral perfusion. Moreover, due to the loss of the protective function of the blood-brain barrier (BBB), impaired clearance of excess neurotoxic amyloid beta (Aβ) occurs, causing vascular perturbation and diminished cognitive functioning. The relationship between the prevalence of AD and vascular risk factors is complex and not fully understood...
November 25, 2016: Vascular Pharmacology
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