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https://www.readbyqxmd.com/read/30016687/recent-advances-in-the-mechanisms-of-neuroinflammation-and-their-role-in-neurodegeneration
#1
REVIEW
Rituraj Niranjan
Neuroinflammation is associated with the pathogenesis of many neurological disorders including Parkinson's disease, Alzheimer's disease, Amyotrophic lateral sclerosis and Huntington disease. Current studies in this area have advanced the mechanism of neuroinflammation and its role in neurodegeneration. Studies from epidemiologic, clinical and animal models also contributed in the various new mechanisms of neuroinflammation. In this line, activation of monocytes is an important emerging mechanism that has a, profound role in neuroinflammation and neurodegeneration...
July 14, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/30016667/the-nmda-receptor-antagonist-radiprodil-reverses-the-synaptotoxic-effects-of-different-amyloid-beta-a%C3%AE-species-on-long-term-potentiation-ltp
#2
Gerhard Rammes, Franziska Seeser, Korinna Mattusch, Kaichuan Zhu, Laura Haas, Markus Kummer, Michael Heneka, Jochen Herms, Chris G Parsons
Aβ1-42 is well accepted to be a primary early pathogenic agent in Alzheimer's disease (AD). However, other amyloid peptides are now gaining considerable attention as potential key participants in AD due to their proposed higher neuronal toxicity. Impairment of the glutamatergic system is also widely accepted to be associated with pathomechanisms underlying AD. There is ample evidence that Aβ1-42 affects GLUN2B subunit containing N-methyl-D-aspartate receptor function and abolishes the induction of long term potentiation (LTP)...
July 14, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30016644/activities-bioavailability-and-metabolism-of-lipids-from-structural-membranes-and-oils-promising-research-on-mild-cognitive-impairment
#3
REVIEW
Antonio Pérez-Gálvez, Manuel Jarén-Galán, Juan Garrido-Fernández, M Visitacion Calvo, Francesco Visioli, Javier Fontecha
Concomitant with increased lifespan, large segments of the population are experiencing cognitive decline, which might progress to Alzheimer's disease (AD). Currently, there is no cure for AD and, once the neurodegenerative disorders are established, patients use pharmacologic therapy to slow the progression of the symptoms and require appropriate care to manage their condition. The preclinical stage of neural degeneration that progress through mild cognitive impairment (MCI) before the onset of AD is when it might be possible to introduce behavioral changes and pharma-nutritional interventions that modify the risk factors of MCI conversion to AD...
July 14, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30016458/%C3%AE-amyloid-induces-pathology-related-patterns-of-tau-hyperphosphorylation-at-synaptic-terminals
#4
Hsin-Yi Wu, Po-Cheng Kuo, Yi-Ting Wang, Hao-Tai Lin, Allyson D Roe, Bo Y Wang, Chia-Li Han, Bradley T Hyman, Yu-Ju Chen, Hwan-Ching Tai
A synergy between β-amyloid (Aβ) and tau appears to occur in Alzheimer disease (AD), but the mechanisms of interaction, and potential locations, are little understood. This study investigates the possibility of such interactions within the cortical synaptic compartments of APP/PS1 mice. We used label-free quantitative mass spectrometry to study the phosphoproteome of synaptosomes, covering 2400 phosphopeptides and providing an unbiased survey of phosphorylation changes associated with amyloid pathology. Hyperphosphorylation was detected on 36 synaptic proteins, many of which are associated with the cytoskeleton...
July 16, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/30016411/molecular-properties-underlying-regional-vulnerability-to-alzheimer-s-disease-pathology
#5
Michel J Grothe, Jorge Sepulcre, Gabriel Gonzalez-Escamilla, Irina Jelistratova, Michael Schöll, Oskar Hansson, Stefan J Teipel
Amyloid deposition and neurofibrillary degeneration in Alzheimer's disease specifically affect discrete neuronal systems, but the underlying mechanisms that render some brain regions more vulnerable to Alzheimer's disease pathology than others remain largely unknown. Here we studied molecular properties underlying these distinct regional vulnerabilities by analysing Alzheimer's disease-typical neuroimaging patterns of amyloid deposition and neurodegeneration in relation to regional gene expression profiles of the human brain...
July 16, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/30015864/oxidative-stress-in-electrohypersensitivity-self%C3%A2-reporting-patients-results-of-a-prospective-in-vivo-investigation-with-comprehensive-molecular-analysis
#6
Philippe Irigaray, Daniela Caccamo, Dominique Belpomme
A total of 32 electrohypersensitivity (EHS) self‑reporting patients were serially included in the present prospective study for oxidative stress and antioxidative stress response assessment. All thiobarbituric acid‑reactive substances (TBARs) were measured in the plasma, particularly malondialdehyde (MDA) for lipid peroxidation; additional measurements included total thiol group molecules, reduced glutathione (GSH), oxidized glutathione (GSSG) for oxidative stress assessment and nitrotyrosine, a marker of peroxynitrite‑induced oxidative/nitrosative stress...
July 12, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/30015476/peptide-based-acetylcholinesterase-inhibitor-crosses-blood-brain-barrier-and-promotes-neuroprotection
#7
Prasenjit Mondal, Varsha Gupta, Gaurav Das, Krishnangsu Pradhan, Juhee Khan, Prabir Kumar Gharai, Surajit Ghosh
Design and development of acetylcholinesterase (AChE) inhibitor has tremendous implications in the treatment of Alzheimer's disease (AD). Here, we have adopted a computational approach for designing of peptide based AChE inhibitor from its active site. We identified an octapeptide, which interacts with the catalytic anionic site (CAS) of AChE enzyme and inhibits its activity. Interestingly, this peptide also inhibits amyloid aggregation through interacting at the 17-21 region of amyloid-beta (Aβ) and stabilizes microtubules by interacting with tubulin as well...
July 17, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30015245/neuronal-calcium-signaling-via-store-operated-channels-in-health-and-disease
#8
REVIEW
Tomasz Wegierski, Jacek Kuznicki
Store-operated calcium entry (SOCE) is the flow of calcium ions (Ca2+ ) into cells in response to the depletion of intracellular Ca2+ stores that reside predominantly in the endoplasmic reticulum (ER). The role of SOCE has been relatively well understood for non-excitable cells. It is mediated mostly by the ER Ca2+ sensor STIM1 and plasma membrane Ca2+ channel Orai1 and serves to sustain Ca2+ signaling and refill ER Ca2+ stores. In contrast, because of the complexity of Ca2+ influx mechanisms that are present in excitable cells, our knowledge about the function of neuronal SOCE (nSOCE) is still nascent...
July 7, 2018: Cell Calcium
https://www.readbyqxmd.com/read/30015143/an-antibody-based-platform-for-melatonin-quantification
#9
Laís C Brazaca, Camila B Bramorski, Juliana Cancino-Bernardi, Sanseray da Silveira Cruz-Machado, Regina P Markus, Bruno C Janegitz, Valtencir Zucolotto
Melatonin, the 'chemical signal of darkness', is responsible to regulate biological rhythms and different physiological processes. It is mainly produced by the pineal gland as a hormone in a rhythmic daily basis, but it may also be synthesized by other tissues, such as immune cells, under inflammatory conditions. Its abnormal circulating levels have been related to several diseases such as type 2 diabetes, Alzheimer's disease and some types of cancer. Currently, melatonin is exclusively quantified by ELISA or radioimmunoassays, which although are very sensitive techniques and present low detection limits, usually require specialized personal and equipment, restricting the tests to a limited number of patients...
July 7, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/30015036/estimates-of-age-related-memory-decline-are-inflated-by-unrecognized-alzheimer-s-disease
#10
Karra D Harrington, Adrian Schembri, Yen Ying Lim, Christa Dang, David Ames, Jason Hassenstab, Simon M Laws, Stephanie Rainey-Smith, Joanne Robertson, Christopher C Rowe, Hamid R Sohrabi, Olivier Salvado, Michael Weinborn, Victor L Villemagne, Colin L Masters, Paul Maruff
Cognitive decline is considered an inevitable consequence of aging; however, estimates of cognitive aging may be influenced negatively by undetected preclinical Alzheimer's disease (AD). This study aimed to determine the extent to which estimates of cognitive aging were biased by preclinical AD. Cognitively normal older adults (n = 494) with amyloid-β status determined from positron emission tomography neuroimaging underwent serial neuropsychological assessment at 18-month intervals over 72 months. Estimates of the effects of age on verbal memory, working memory, executive function, and processing speed were derived using linear mixed models...
June 11, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/30015035/brain-regional-synchronous-activity-predicts-tauopathy-in-3%C3%A3-tgad-mice
#11
Dong Liu, Hanbing Lu, Elliot Stein, Zhujuan Zhou, Yihong Yang, Mark P Mattson
Alzheimer's disease (AD) is characterized by progressive cognitive impairment and by extensive neuronal loss associated with extracellular amyloid β-peptide (Aβ) plaques and intraneuronal tau pathology in temporal and parietal lobes. AD patients are at increased risk for epileptic seizures, and data from experimental models of AD suggest that aberrant neuronal network activity occurs early in the disease process before cognitive deficits and neuronal degeneration. The contributions of Aβ and/or tau pathologies to dysregulation of neuronal network activity are unclear...
June 21, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/30014763/chemogenomics-system-pharmacology-mapping-of-potential-drug-targets-for-treatment-of-traumatic-brain-injury
#12
Lirong Wang, Shifan Ma, Ziheng Hu, Terence Francis McGuire, Xiangqun Xie
Traumatic brain injury (TBI) is associated with high mortality and morbidity. Though the death rate of initial trauma has dramatically decreased, no drug has been developed for the secondary injury caused by TBI. TBI appears to be a predisposing risk factor of Alzheimer's disease (AD), while the molecular mechanisms remain unknown. In this study, we have conducted a research investigation of computational chemogenomics system pharmacology (CSP) to identify potential drug targets for TBI treatment. TBI-induced transcriptional profiles were compared with those induced by genetic or chemical perturbations, including TBI drugs in clinical trials...
July 17, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/30014757/a-small-molecule-spinogenic-compound-enhances-functional-outcome-and-dendritic-spine-plasticity-in-a-rat-model-of-traumatic-brain-injury
#13
Yanlu Zhang, Michael Chopp, Christopher S Rex, Vincent F Simmon, Stella T Sarraf, Zheng Gang Zhang, Asim Mahmood, Ye Xiong
The tetra (ethylene glycol) derivative of benzothiazole aniline (SPG101) has been shown to improve dendritic spine density and cognitive memory in the triple transgenic mouse model of Alzheimer's disease (AD) when administered intraperitoneally. The present study was designed to investigate the therapeutic effects of SPG101 on dendritic spine density and morphology, and sensorimotor and cognitive functional recovery in a rat model of traumatic brain injury (TBI) induced by controlled cortical impact (CCI). Young adult male Wistar rats with CCI were randomly divided into the following 2 groups (n=7/group): 1) Vehicle, and 2) SPG101...
July 17, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/30014576/intracerebroventricular-streptozotocin-induced-alzheimer-s-disease-like-sleep-disorders-in-rats-role-of-the-gabaergic-system-in-the-parabrachial-complex
#14
Su-Ying Cui, Jin-Zhi Song, Xiang-Yu Cui, Xiao Hu, Yu-Nu Ma, Yu-Tong Shi, Ying Luo, Yan-Ru Ge, Hui Ding, Hui Ye, Yong-He Zhang
AIM: Sleep disorders are common in Alzheimer's disease (AD) and assumed to directly influence cognitive function and disease progression. This study evaluated sleep characteristics in a rat model of AD that was induced by intracerebroventricular streptozotocin (STZ) administration and assessed the possible underlying mechanisms. METHODS: Cognition ability was assessed in the Morris water maze in rats. Sleep parameters were analyzed by electroencephalographic and electromyographic recordings...
July 16, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/30014553/effect-of-bdnfval66met-on-disease-markers-in-dominantly-inherited-ad
#15
Yen Ying Lim, Jason Hassenstab, Alison Goate, Anne M Fagan, Tammie L S Benzinger, Carlos Cruchaga, Eric McDade, Jasmeer Chhatwal, Johannes Levin, Martin R Farlow, Neill R Graff-Radford, Christoph Laske, Colin L Masters, Stephen Salloway, Peter Schofield, John C Morris, Paul Maruff, Randall J Bateman
OBJECTIVE: Previous studies suggest that the brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism may influence symptom onset in Alzheimer's disease (AD). Our recent cross-sectional findings suggest that Met66 may influence clinical expression in dominantly inherited AD (DIAD) through its effects on tau. However, it remains unclear whether carriage of Met66 in DIAD results in faster increases in CSF tau and ptau181 , and whether these increases are associated with accelerated brain volume loss and memory decline...
July 16, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/30014506/multi-crossover-randomized-controlled-trial-designs-in-alzheimer-s-disease
#16
Steven E Arnold, Rebecca A Betensky
Conventional parallel group randomized controlled clinical trials (RCT) in Alzheimer's disease (AD) are too large, long, expensive and insensitive to clinical change to meet the urgent need for an effective treatment. While providing good evidence for a treatment's benefit, parallel group RCTs in AD must have very large samples and broad measures of change to accommodate the marked heterogeneity of demographics, genetics, symptoms, pathophysiologies, comorbidities and rates of progression. Multi-crossover, placebo-controlled, double-blind RCTs, including those with sample sizes as small as a single subject ("N-of-1"), are robust designs wherein subjects serve as their own controls in repeated blocks of randomly sequenced crossover treatments...
July 16, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/30014355/oxidative-stress-and-neurodegeneration-the-involvement-of-iron
#17
REVIEW
Alessia Carocci, Alessia Catalano, Maria Stefania Sinicropi, Giuseppe Genchi
Many evidences indicate that oxidative stress plays a significant role in a variety of human disease states, including neurodegenerative diseases. Iron is an essential metal for almost all living organisms due to its involvement in a large number of iron-containing proteins and enzymes, though it could be also toxic. Actually, free iron excess generates oxidative stress, particularly in brain, where anti-oxidative defences are relatively low. Its accumulation in specific regions is associated with pathogenesis in a variety of neurodegenerative diseases (i...
July 16, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/30014313/visualization-of-ischemic-stroke-related-changes-on-18-f-thk-5351-positron-emission-tomography
#18
Kuo-Lun Huang, Jung-Lung Hsu, Kun-Ju Lin, Chien-Hung Chang, Yi-Ming Wu, Ting-Yu Chang, Yeu-Jhy Chang, Chi-Hung Liu, Meng-Yang Ho, Shiaw-Pyng Wey, Tzu-Chen Yen, Nobuyuki Okamura, Ing-Tsung Hsiao, Tsong-Hai Lee
BACKGROUND: The 18 F-THK-5351 radiotracer has been used to detect the in vivo tau protein distribution in patients with tauopathy, such as Alzheimer's disease and corticobasal syndrome. In addition, 18 F-THK-5351 can also monitor neuroinflammatory process due to high affinity to astrogliosis. We aimed to explore 18 F-THK-5351 distribution patterns and characteristics in patients with recent ischemic stroke. RESULTS: Fifteen patients received 18 F-THK-5351 positron emission tomography (PET) and diffusion tensor imaging (DTI) approximately 3 months after ischemic stroke...
July 16, 2018: EJNMMI Research
https://www.readbyqxmd.com/read/30014221/structural-effects-of-methylglyoxal-glycation-a-study-on-the-model-protein-mnei
#19
Serena Leone, Jole Fonderico, Chiara Melchiorre, Andrea Carpentieri, Delia Picone
The reaction of free amino groups in proteins with reactive carbonyl species, known as glycation, leads to the formation of mixtures of products, collectively referred to as advanced glycation endproducts (AGEs). These compounds have been implicated in several important diseases, but their role in pathogenesis and clinical symptoms' development is still debated. Particularly, AGEs are often associated to the formation of amyloid deposits in conformational diseases, such as Alzheimer's and Parkinson's disease, and it has been suggested that they might influence the mechanisms and kinetics of protein aggregation...
July 16, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/30014145/assessing-synaptic-density-in-alzheimer-disease-with-synaptic-vesicle-glycoprotein-2a-positron-emission-tomographic-imaging
#20
Ming-Kai Chen, Adam P Mecca, Mika Naganawa, Sjoerd J Finnema, Takuya Toyonaga, Shu-Fei Lin, Soheila Najafzadeh, Jim Ropchan, Yihuan Lu, Julia W McDonald, Hannah R Michalak, Nabeel B Nabulsi, Amy F T Arnsten, Yiyun Huang, Richard E Carson, Christopher H van Dyck
Importance: Synaptic loss is well established as the major structural correlate of cognitive impairment in Alzheimer disease (AD). The ability to measure synaptic density in vivo could accelerate the development of disease-modifying treatments for AD. Synaptic vesicle glycoprotein 2A is an essential vesicle membrane protein expressed in virtually all synapses and could serve as a suitable target for synaptic density. Objective: To compare hippocampal synaptic vesicle glycoprotein 2A (SV2A) binding in participants with AD and cognitively normal participants using positron emission tomographic (PET) imaging...
July 16, 2018: JAMA Neurology
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