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https://www.readbyqxmd.com/read/28343297/association-of-the-cx3cr1-v249i-variant-with-neurofibrillary-pathology-progression-in-late-onset-alzheimer-s-disease
#1
Alan López-López, Ellen Gelpi, Diana Maria Lopategui, Jose M Vidal-Taboada
Neuroinflammation and microglial dysfunction have a prominent role in the pathogenesis of late-onset Alzheimer's disease (LOAD). CX3CR1 is a microglia-specific gene involved in microglia-neuron crosstalk and neuroinflammation. Numerous evidence show the involvement of CX3CR1 in AD. The aim of this study was to investigate if some functional genetic variants of this gene could influence on LOAD's outcome, in a neuropathologically confirmed Spanish cohort. We designed an open, pragmatic, case-control retrospective study including a total of 475 subjects (205 pathologically confirmed AD cases and 270 controls)...
March 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28343095/ion-mobility-mass-spectrometry-and-orthogonal-gas-phase-techniques-to-study-amyloid-formation-and-inhibition
#2
REVIEW
Waldemar Hoffmann, Gert von Helden, Kevin Pagel
Amyloidogenic peptide oligomers are responsible for a variety of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Due to their dynamic, polydisperse, and polymorphic nature, these oligomers are very challenging to characterize using traditional condensed-phase methods. In the last decade, ion mobility-mass spectrometry (IM-MS) and related gas-phase techniques have emerged as a powerful alternative to disentangle the structure and assembly characteristics of amyloid forming systems. This review highlights recent advances in which IM-MS was used to characterize amyloid oligomers and their underlying assembly pathway...
March 23, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28342971/a-novel-dual-glp-1-gip-receptor-agonist-alleviates-cognitive-decline-by-re-sensitizing-insulin-signaling-in-the-alzheimer-icv-stz-rat-model
#3
Lijuan Shi, Zhihua Zhang, Lin Li, Christian Hölscher
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, accompanied by memory loss and cognitive impairments, and there is no effective treatment for it at present. Since type 2 diabetes (T2DM) has been identified as a risk factor for AD, the incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), promising antidiabetic agents for the treatment of type 2 diabetes, have been tested in models of neurodegenerative disease including AD and achieved good results...
March 22, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28342882/functional-neuroimaging-findings-in-healthy-middle-aged-adults-at-risk-of-alzheimer-s-disease
#4
REVIEW
Mirette Habib, Elijah Mak, Silvy Gabel, Li Su, Guy Williams, Adam Waldman, Katie Wells, Karen Ritchie, Craig Ritchie, John T O'Brien
It is well established that the neurodegenerative process of Alzheimer's disease (AD) begins many years before symptom onset. This preclinical phase provides a crucial time-window for therapeutic intervention, though this requires biomarkers that could evaluate the efficacy of future disease-modification treatments in asymptomatic individuals. The last decade has witnessed a proliferation of studies characterizing the temporal sequence of the earliest functional and structural brain imaging changes in AD. These efforts have focused on studying individuals who are highly vulnerable to develop AD, such as those with familial genetic mutations, susceptibility genes (i...
March 22, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28342757/role-of-enzymatic-free-radical-scavengers-in-management-of-oxidative-stress-and-autoimmune-disorders
#5
REVIEW
Shikha Srivastava, Deependra Singh, Satish Patel, Manju R Singh
Autoimmune disorders are distinct with over production and accumulation of free radicals due to its undisclosed genesis. The cause of numerous disorders as cancer, arthritis, psoriasis, diabetes, alzheimer's, cardiovascular disease, Parkinson's, respiratory distress syndrome, colitis, crohn's, pulmonary fibrosis, obesity and ageing have been associated with immune dysfunction and oxidative stress. In an oxidative stress, reactive oxygen species generally provoke the series of oxidation at cellular level. The buildup of free radicals in turn triggers various inflammatory cells causing release of various inflammatory interleukins, cytokines, chemokines, and tumor necrosis factors which mediate signal transduction and transcription pathways as nuclear factor- kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1 (HIF-1α) and nuclear factor-erythroid 2-related factor (Nrf2)...
March 22, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28342697/recent-publications-from-the-alzheimer-s-disease-neuroimaging-initiative-reviewing-progress-toward-improved-ad-clinical-trials
#6
REVIEW
Michael W Weiner, Dallas P Veitch, Paul S Aisen, Laurel A Beckett, Nigel J Cairns, Robert C Green, Danielle Harvey, Clifford R Jack, William Jagust, John C Morris, Ronald C Petersen, Andrew J Saykin, Leslie M Shaw, Arthur W Toga, John Q Trojanowski
INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the 450+ publications using ADNI data during 2014 and 2015. METHODS: We used standard searches to find publications using ADNI data. RESULTS: (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses...
March 22, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28342649/the-prognosis-of-dementia-with-lewy-bodies
#7
REVIEW
Christoph Mueller, Clive Ballard, Anne Corbett, Dag Aarsland
Dementia with Lewy bodies is the second most common form of neurodegenerative dementia, yet scarce evidence is available about its prognosis and natural history, which are crucial to inform clinical practice and research. Patients with dementia with Lewy bodies might have a less favourable prognosis, with accelerated cognitive decline, shorter lifespan, and increased admission to residential care than patients with Alzheimer's disease. Health-care costs and, importantly, caregiver burden, are also reported to be higher in dementia with Lewy bodies than in Alzheimer's disease...
March 22, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28342386/association-between-environmental-factors-and-emergency-hospital-admissions-due-to-alzheimer-s-disease-in-madrid
#8
D R Culqui, C Linares, C Ortiz, R Carmona, J Díaz
INTRODUCTION: There are scarce studies of time series that analysed the short-term association between emergency hospital admissions due to Alzheimer's disease (AD) and environmental factors. The objective is to analyse the effect of heat waves, noise and air pollutants on urgent hospital admissions due to AD in Madrid. METHODS: Longitudinal ecological time series study was performed. The dependent variable was the emergency AD hospital admissions occurred in Madrid during the period 2001-2009...
March 22, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28340083/evaluating-the-patterns-of-aging-related-tau-astrogliopathy-unravels-novel-insights-into-brain-aging-and-neurodegenerative-diseases
#9
Gabor G Kovacs, John L Robinson, Sharon X Xie, Edward B Lee, Murray Grossman, David A Wolk, David J Irwin, Dan Weintraub, Christopher F Kim, Theresa Schuck, Ahmed Yousef, Stephanie T Wagner, Eunran Suh, Vivianna M Van Deerlin, Virginia M-Y Lee, John Q Trojanowski
The term "aging-related tau astrogliopathy" (ARTAG) describes pathological accumulation of abnormally phosphorylated tau protein in astrocytes. We evaluated the correlates of ARTAG types (i.e., subpial, subependymal, white and gray matter, and perivascular) in different neuroanatomical regions. Clinical, neuropathological, and genetic (eg, APOE ε4 allele, MAPT H1/H2 haplotype) data from 628 postmortem brains from subjects were investigated; most of the patients had been longitudinally followed at the University of Pennsylvania...
March 14, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28339396/modulation-of-a%C3%AE-pp-and-gsk3%C3%AE-by-endoplasmic-reticulum-stress-and-involvement-in-alzheimer-s-disease
#10
Xin-Jun Liu, Jun Wei, Ying-Hui Shang, Han-Chang Huang, Feng-Xue Lao
Alzheimer's disease (AD) is a dementia disease with neuronal loss and synaptic impairment. This impairment is caused, at least partly, by the generation of two main AD hallmarks, namely the hyperphosphorylated tau protein comprising neurofibrillary tangles and senile plaques containing amyloid-β (Aβ) peptides. The amyloid-β protein precursor (AβPP) and glycogen synthase kinase-3β (GSK3β) are two main proteins associated with AD and are closely correlated with these hallmarks. Recently, both of the proteins were reported to be modulated by endoplasmic reticulum stress (ERS) and are involved in the pathogenesis of AD...
March 20, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28339060/chronological-changes-in-the-expression-of-phosphorylated-tau-and-5%C3%A2-amp%C3%A2-activated-protein-kinase-in-the-brain-of-senescence%C3%A2-accelerated-p8-mice
#11
Hak-Su Kim, Sohee Moon, Sujin Kim, Min-Jae Lee, Min Hwa Suk, Dong-Ho Park, Dong Wun Shin, Chang-Shin Park, Ju-Hee Kang
Senescence-accelerated mouse prone 8 (SAMP8), a non‑transgenic animal model used for researching sporadic Alzheimer's disease (AD), presents AD pathologies and overall dysregulation in brain energy metabolism, which is one of the early pathogenic characteristics of AD. In the present study, the authors examined chronological changes in the expression patterns of phosphorylated tau and of proteins related to energy metabolism to evaluate the association of tau phosphorylation and metabolism, using young‑ (2‑months‑old), middle‑ (5‑months‑old) and old‑aged (10‑months‑old) SAMP8...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338847/paradigm-shift-from-diagnosing-patients-based-on-common-symptoms-to-categorizing-patients-into-subtypes-with-different-pathogenic-mechanisms-to-guide-treatment-for-alzheimer-s-disease
#12
Keiro Shirotani, Masashi Asai, Nobuhisa Iwata
Alzheimer's disease (AD) is a major cause of dementia in the elderly, and the number of AD patients is rapidly growing as life expectancy increases. However, disease-modifying drugs are not yet available. According to the amyloid hypothesis, disease onset is triggered by aggregation and accumulation of amyloid-β peptide, followed by formation of neurofibrillary tangles composed of hyperphosphorylated tau, and synaptic loss/neuronal cell death leading to dementia. Based on this hypothesis, various clinical trials for treatment of AD have been conducted, but most were discontinued due to failure to achieve cognitive improvement or appearance of adverse effects...
March 7, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28338621/optimized-4-5-diarylimidazoles-as-potent-selective-inhibitors-of-protein-kinase-ck1%C3%AE-and-their-structural-relation-to-p38%C3%AE-mapk
#13
Jakob Halekotte, Lydia Witt, Chiara Ianes, Marc Krüger, Mike Bührmann, Daniel Rauh, Christian Pichlo, Elena Brunstein, Andreas Luxenburger, Ulrich Baumann, Uwe Knippschild, Joachim Bischof, Christian Peifer
The involvement of protein kinase CK1δ in the pathogenesis of severe disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, familial advanced sleep phase syndrome, and cancer has dramatically increased interest in the development of effective small molecule inhibitors for both therapeutic application and basic research. Unfortunately, the design of CK1 isoform-specific compounds has proved to be highly complicated due to the existence of six evolutionarily conserved human CK1 members that possess similar, different, or even opposite physiological and pathophysiological implications...
March 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28338146/a-gold-nanoparticle-mediated-rapid-in-vitro-assay-of-anti-aggregation-reagents-for-amyloid-%C3%AE-and-its-validation
#14
Hye Young Kim, Donghee Lee, Kwon-Yul Ryu, Inhee Choi
Herein, we report a rapid in vitro assay of amyloid β anti-aggregation reagents using gold nanoparticles as nucleation cores and optical reporters. Based on the colorimetric responses observed with the naked eye, effective anti-aggregation reagents were rapidly (<15 min) distinguished. For these reagents, conventional methods showed fewer amyloid β aggregates and an increased viability of neuroblastoma cells after treatment. We envision that our proposed method will facilitate the discovery of efficient drug components for the treatment of Alzheimer's disease...
March 24, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28338075/alzheimer-disease-localized-proteomics-distinguishes-ad-subtypes
#15
Heather Wood
No abstract text is available yet for this article.
March 24, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28338052/dissociable-diffusion-mri-patterns-of-white-matter-microstructure-and-connectivity-in-alzheimer-s-disease-spectrum
#16
Nhat Trung Doan, Andreas Engvig, Karin Persson, Dag Alnæs, Tobias Kaufmann, Jaroslav Rokicki, Aldo Córdova-Palomera, Torgeir Moberget, Anne Brækhus, Maria Lage Barca, Knut Engedal, Ole A Andreassen, Geir Selbæk, Lars T Westlye
Recent efforts using diffusion tensor imaging (DTI) have documented white matter (WM) alterations in Alzheimer's disease (AD). The full potential of whole-brain DTI, however, has not been fully exploited as studies have focused on individual microstructural indices independently. In patients with AD (n = 79), mild (MCI, n = 55) and subjective (SCI, n = 30) cognitive impairment, we applied linked independent component analysis (LICA) to model inter-subject variability across five complementary DTI measures (fractional anisotropy (FA), axial/radial/mean diffusivity, diffusion tensor mode), two crossing fiber measures estimated using a multi-compartment crossing-fiber model reflecting the volume fraction of the dominant (f1) and non-dominant (f2) diffusion orientation, and finally, connectivity density obtained from full-brain probabilistic tractography...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337747/structure-dependent-effects-of-amyloid-%C3%AE-on-long-term-memory-in-lymnaea-stagnalis
#17
Lenzie Ford, Michael Crossley, Devkee M Vadukul, György Kemenes, Louise C Serpell
Amyloid-β (Aβ) peptides are implicated in the causation of memory loss, neuronal impairment, and neurodegeneration in Alzheimer's disease. Our recent work revealed that Aβ 1-42 and Aβ 25-35 inhibit long-term memory (LTM) recall in Lymnaea stagnalis (pond snail) in the absence of cell death. Here, we report the characterization of the active species prepared under different conditions, describe which Aβ species is present in brain tissue during the behavioral recall time point and relate the sequence and structure of the oligomeric species to the resulting neuronal properties and effect on LTM...
March 24, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28337659/a20-in-multiple-sclerosis-and-parkinson-s-disease-clue-to-a-common-dysregulation-of-anti-inflammatory-pathways
#18
Simona Perga, Serena Martire, Francesca Montarolo, Nicole D Navone, Andrea Calvo, Giuseppe Fuda, Alberto Marchet, Daniela Leotta, Adriano Chiò, Antonio Bertolotto
Chronic inflammation significantly contributes to the pathogenesis of several neurodegenerative disorders. In physiological conditions, a chronic inflammatory state is prevented through the termination of the acute inflammatory response once the triggering insult is eliminated. Several mechanisms regulate the resolution of inflammation. Among these, a potent inhibitor of the pro-inflammatory NF-kB signaling known as A20 has emerged as a key player. Recent studies have shown reduced blood levels of A20 in the patients of diverse chronic inflammatory diseases...
March 23, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28337631/upregulation-of-mineralocorticoid-receptor-in-the-hypothalamus-associated-with-a-high-anxiety-like-level-in-apolipoprotein-e4-transgenic-mice
#19
Fan-Tao Meng, Jun Zhao, Hui Fang, Li-Feng Zhang, Hui-Mei Wu, Ya-Jing Liu
Anxiety symptoms occur in a large portion of Alzheimer's disease (AD) patients. ApolipoproteinE-4 (ApoE ε4 allele), a risk factor for AD, has been recognized as an important contributor to psychiatric disorders. In the present study, we aimed to investigate the corticosterone level in relation to anxiety-like behavior changes in transgenic male mice with different glial fibrillary acidic protein (GFAP)-ApoE isoforms. GFAP-ApoE4 transgenic mice aged 3 months showed higher anxiety-like behavior in open field, light-dark box and elevated plus maze tasks compared with that of age-matched GFAP-ApoE3 mice...
March 24, 2017: Behavior Genetics
https://www.readbyqxmd.com/read/28337562/bace2-suppression-promotes-%C3%AE-cell-survival-and-function-in-a-model-of-type-2-diabetes-induced-by-human-islet-amyloid-polypeptide-overexpression
#20
Gema Alcarraz-Vizán, Carlos Castaño, Montse Visa, Joel Montane, Joan-Marc Servitja, Anna Novials
BACE2 (β-site APP-cleaving enzyme 2) is a protease expressed in the brain, but also in the pancreas, where it seems to play a physiological role. Amyloidogenic diseases, including Alzheimer's disease and type 2 diabetes (T2D), share the accumulation of abnormally folded and insoluble proteins that interfere with cell function. In T2D, islet amyloid polypeptide (IAPP) deposits have been shown to be a pathogenic key feature of the disease. The aim of the present study was to investigate the effect of BACE2 modulation on β-cell alterations in a mouse model of T2D induced by IAPP overexpression...
March 23, 2017: Cellular and Molecular Life Sciences: CMLS
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