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https://www.readbyqxmd.com/read/29036813/association-between-later-life-lifestyle-factors-and-alzheimer-s-disease-biomarkers-in-non-demented-individuals-a-longitudinal-descriptive-cohort-study
#1
Babette L R Reijs, Stephanie J B Vos, Hilkka Soininen, Jyrki Lötjonen, Juha Koikkalainen, Maria Pikkarainen, Anette Hall, Ritva Vanninen, Yawu Liu, Sanna-Kaisa Herukka, Yvonne Freund-Levi, Giovanni B Frisoni, Lutz Frölich, Flavio Nobili, Marcel Olde Rikkert, Luiza Spiru, Magda Tsolaki, Åsa K Wallin, Philip Scheltens, Frans Verhey, Pieter Jelle Visser
BACKGROUND: Lifestyle factors have been associated with the risk of dementia, but the association with Alzheimer's disease (AD) remains unclear. OBJECTIVE: To examine the association between later life lifestyle factors and AD biomarkers (i.e., amyloid-β 1-42 (Aβ42) and tau in cerebrospinal fluid (CSF), and hippocampal volume) in individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). In addition, to examine the effect of later life lifestyle factors on developing AD-type dementia in individuals with MCI...
October 11, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29036434/novel-mechanisms-of-eif2b-action-and-regulation-by-eif2%C3%AE-phosphorylation
#2
Andrew M Bogorad, Kai Ying Lin, Assen Marintchev
Eukaryotic translation initiation factor 2 (eIF2) is a heterotrimeric GTPase, which plays a critical role in protein synthesis regulation. eIF2-GTP binds Met-tRNAi to form the eIF2-GTP•Met-tRNAi ternary complex (TC), which is recruited to the 40S ribosomal subunit. Following GTP hydrolysis, eIF2-GDP is recycled back to TC by its guanine nucleotide exchange factor (GEF), eIF2B. Phosphorylation of the eIF2α subunit in response to various cellular stresses converts eIF2 into a competitive inhibitor of eIF2B, which triggers the integrated stress response (ISR)...
September 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29036304/il-1r-and-myd88-signaling-in-cd4-t-cells-promote-th17-immunity-and-atherosclerosis
#3
Daniel Engelbertsen, Sara Rattik, Maria Wigren, Jenifer Vallejo, Goran Marinkovic, Alexandru Schiopu, Harry Björkbacka, Jan Nilsson, Eva Bengtsson
Aims: The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper subsets. In this study we tested the roles of IL-1R1 and MyD88 signaling in CD4+ T cells in atherosclerosis. Methods and results: We transferred apoe-/-myd88+/+or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared to mice given apoe-/-myd88+/+ CD4+ T cells...
September 28, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29035447/porphyromonas-gingivalis-infection-accelerates-atherosclerosis-mediated-by-oxidative-stress-and-inflammatory-responses-in-apoe-mice
#4
Yan Xuan, Qiao Shi, Guo-Jing Liu, Qing-Xian Luan, Yu Cai
BACKGROUND: The periodontal pathogen Porphyromonas gingivalis (P. gingivalis) has been proven to accelerate the development of atherosclerosis in apolipoprotein E (ApoE)-deficient mice. In this study, we used an ApoE knockout (ApoE-/-) mouse model with chronic intravenous infection with P. gingivalis to investigate the possible mechanisms of P. gingivalis-induced atherosclerosis. METHODS: Eight-week-old ApoE-/- mice were randomly assigned to two groups: (a) ApoE-/- + PBS (n = 8); (b) ApoE-/- + P...
October 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/29034886/generation-and-characterization-of-human-induced-pluripotent-stem-cell-hipsc-lines-from-an-alzheimer-s-disease-asui001-a-and-non-demented-control-asui002-a-patient-homozygous-for-the-apolipoprotein-e4-apoe4-risk-variant
#5
Nicholas Brookhouser, Ping Zhang, Richard Caselli, Jean J Kim, David A Brafman
Although the majority of late-onset Alzheimer's disease (AD) patients are labeled sporadic, multiple genetic risk variants have been identified, the most powerful and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene. Here, we generated human induced pluripotent stem cell (hiPSC) lines from the peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient [ASUi001-A] and a non-demented control (NDC) patient [ASUi002-A] homozygous for the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed pluripotency markers, exhibited a normal karyotype, and demonstrated the ability to differentiate into cells representative of the three germ layers...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29034839/pharmacogenetics-of-angiotensin-converting-enzyme-inhibitors-in-patients-with-alzheimer-s-disease-dementia
#6
Fabricio Ferreira de Oliveira, Elizabeth Suchi Chen, Marilia Cardoso Smith, Paulo Henrique Ferreira Bertolucci
BACKGROUND: While the angiotensin-converting enzyme degrades amyloid-β, angiotensin-converting enzyme inhibitors (ACEis) may slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer's disease dementia (AD). We aimed to investigate whether ACE gene polymorphisms rs1800764 and rs4291 are associated with cognitive and functional change in patients with AD, while also taking APOE haplotypes and anti-hypertensive treatment with ACEis into account for stratification...
October 16, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/29032750/longitudinal-neuropsychological-outcome-in-taiwanese-alzheimer-s-disease-patients-treated-with-medication
#7
Pi-Shan Sung, Meng-Ni Wu, Ping-Song Chou, Hui-Chen Su, Sheng-Hsiang Lin, Yuan-Han Yang
Background The longitudinal change of neuropsychological tests (NPTs) in treated Alzheimer's disease (AD) is essential to understand the interplay of a therapeutic response from medication and a disease decline due to degenerative processes. The aim of our study is to investigate the annual cognitive progression as measured by commonly used NPTs in treated AD patients and to assess the potential predictors of disease progression. Methods Participants (N=455) diagnosed with AD and treated with cholinesterase inhibitors (ChEIs) or memantine at memory clinics in three hospitals in southern Taiwan from January 2009 to December 2014 were enrolled in this prospectively registered study...
October 10, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/29032015/possible-positive-effect-of-the-apoe-%C3%AE%C2%B52-allele-on-cognition-in-early-to-mid-adult-life
#8
I Sinclair Lindsey, Christopher W Pleydell-Pearce, N M Ian Day
BACKGROUND: ε4 allele possession is associated with an increased risk of Alzheimer's disease. Its effects earlier in life are less well understood. Previous studies have reported both detrimental effects and a lack of effect on cognition outside dementia. We used genotype based recall from the ALSPAC study to investigate whether APOE genotype influences cognition in earlier adult life. METHODS: We invited all individuals with the rarer ε22 or ε44 genotypes and equal numbers of those with ε32, ε33 or ε34 APOE genotypes (total n invited =1936, ages 23-67)...
October 11, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29031222/apolipoproteins-adsorption-and-brain-targeting-evaluation-of-baicalin-nanocrystals-modified-by-combination-of-tween80-and-tpgs
#9
Yang Liu, Yueqin Ma, Junnan Xu, Yingchong Chen, Jin Xie, Pengfei Yue, Qin Zheng, Ming Yang
To help baicalin pass across BBB and improve its targeting in brain, we designed a novel formulation strategy of baicalin nanocrystals that preferentially adsorbing apolipoprotein E (ApoE) and repelling protein adsorption of opsonins. Intravenous baicalin nanocrystals suspensions (BCL-NS) modified by different surfactant were prepared by high-pressure homogenization. The targeting potential of surface-modified BCL-NS with mean particles size of about 250nm was assessed by in vitro protein adsorption studies using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), and further evaluated in vivo pharmacokinetics...
October 5, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29030599/genome-wide-meta-analysis-associates-hla-dqa1-drb1-and-lpa-and-lifestyle-factors-with-human-longevity
#10
Peter K Joshi, Nicola Pirastu, Katherine A Kentistou, Krista Fischer, Edith Hofer, Katharina E Schraut, David W Clark, Teresa Nutile, Catriona L K Barnes, Paul R H J Timmers, Xia Shen, Ilaria Gandin, Aaron F McDaid, Thomas Folkmann Hansen, Scott D Gordon, Franco Giulianini, Thibaud S Boutin, Abdel Abdellaoui, Wei Zhao, Carolina Medina-Gomez, Traci M Bartz, Stella Trompet, Leslie A Lange, Laura Raffield, Ashley van der Spek, Tessel E Galesloot, Petroula Proitsi, Lisa R Yanek, Lawrence F Bielak, Antony Payton, Federico Murgia, Maria Pina Concas, Ginevra Biino, Salman M Tajuddin, Ilkka Seppälä, Najaf Amin, Eric Boerwinkle, Anders D Børglum, Archie Campbell, Ellen W Demerath, Ilja Demuth, Jessica D Faul, Ian Ford, Alessandro Gialluisi, Martin Gögele, MariaElisa Graff, Aroon Hingorani, Jouke-Jan Hottenga, David M Hougaard, Mikko A Hurme, M Arfan Ikram, Marja Jylhä, Diana Kuh, Lannie Ligthart, Christina M Lill, Ulman Lindenberger, Thomas Lumley, Reedik Mägi, Pedro Marques-Vidal, Sarah E Medland, Lili Milani, Reka Nagy, William E R Ollier, Patricia A Peyser, Peter P Pramstaller, Paul M Ridker, Fernando Rivadeneira, Daniela Ruggiero, Yasaman Saba, Reinhold Schmidt, Helena Schmidt, P Eline Slagboom, Blair H Smith, Jennifer A Smith, Nona Sotoodehnia, Elisabeth Steinhagen-Thiessen, Frank J A van Rooij, André L Verbeek, Sita H Vermeulen, Peter Vollenweider, Yunpeng Wang, Thomas Werge, John B Whitfield, Alan B Zonderman, Terho Lehtimäki, Michele K Evans, Mario Pirastu, Christian Fuchsberger, Lars Bertram, Neil Pendleton, Sharon L R Kardia, Marina Ciullo, Diane M Becker, Andrew Wong, Bruce M Psaty, Cornelia M van Duijn, James G Wilson, J Wouter Jukema, Lambertus Kiemeney, André G Uitterlinden, Nora Franceschini, Kari E North, David R Weir, Andres Metspalu, Dorret I Boomsma, Caroline Hayward, Daniel Chasman, Nicholas G Martin, Naveed Sattar, Harry Campbell, Tōnu Esko, Zoltán Kutalik, James F Wilson
Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29030451/weighting-and-standardization-of-frequencies-to-determine-prevalence-of-ad-imaging-biomarkers
#11
Rosebud O Roberts, David S Knopman, Jeremy A Syrjanen, Jeremiah A Aakre, Maria Vassilaki, Walter K Kremers, Michelle M Mielke, Mary M Machulda, Jonathan Graff-Radford, Yonas E Geda, Prashanthi Vemuri, Val Lowe, Clifford R Jack, Ronald C Petersen
OBJECTIVE: To estimate the prevalence of elevated brain amyloid and reduced cortical thickness (as a marker for neurodegeneration) in a defined population. METHODS: Mayo Clinic Study of Aging participants underwent MRI to assess a composite Alzheimer disease (AD) signature cortical thickness measure and PET to assess brain amyloid accumulation. Participants were characterized as having elevated amyloid (A+/A-), reduced cortical thickness (N+/N-), and A+N+, A+N-, A-N+, or A-N-...
October 13, 2017: Neurology
https://www.readbyqxmd.com/read/29030246/interaction-of-a-model-apolipoprotein-apolp-iii-with-an-oil-phospholipid-interface
#12
Mona Mirheydari, Elizabeth K Mann, Edgar E Kooijman
Lipid droplets are "small" organelles that play an important role in de novo synthesis of new membrane, and steroid hormones, as well as in energy storage. The way proteins interact specifically with the oil-(phospho-)lipid monolayer interface of lipid droplets is a relatively unexplored but crucial question. Here, we use our home built liquid droplet tensiometer to mimic intracellular lipid droplets and study protein-lipid interactions at this interface. As model neutral lipid binding protein, we use apoLp-III, an amphipathic α-helix bundle protein...
October 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29030241/discovery-of-hidden-allosteric-sites-as-novel-targets-for-allosteric-drug-design
#13
REVIEW
Shaoyong Lu, Mingfei Ji, Duan Ni, Jian Zhang
Hidden allosteric sites, as a novel type of allosteric site, are invisible in ligand-unbound (apo) crystal structures, but can emerge in ligand-bound (holo) crystal structures when a specific ligand binds to, and stabilizes, a unique conformation favored by the ligand. However, the identification of these sites is a significant challenge. Several computational and experimental approaches have been developed to identify such sites in proteins. Here, we outline these approaches, with a focus on examples of the successful use of such techniques...
October 10, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/29029791/in-search-for-globally-disordered-apo-parvalbumins-case-of-parvalbumin-%C3%AE-1-from-coho-salmon
#14
Alisa A Vologzhannikova, Polina A Khorn, Alexei S Kazakov, Ramis G Ismailov, Andrei S Sokolov, Vladimir N Uversky, Eugene A Permyakov, Sergei E Permyakov
Parvalbumin (PA) is a classical EF-hand calcium-binding protein of muscle, neuronal, and other tissues, and a major fish allergen. Although certain apo-PAs lack tertiary structure, functional implications of that feature and its structural prerequisites remain unclear. In a search for unstable PAs, we probed conformational stability of parvalbumin β-1 from coho salmon (csPA), a cold water fish species, using circular dichroism, scanning calorimetry, hydrophobic probe fluorescence, limited proteolysis, chemical crosslinking and dynamic light scattering techniques...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/29029165/depicting-new-pharmacological-strategies-for-familial-hypercholesterolaemia-involving-lipoprotein-a
#15
Alpo Vuorio, Gerald F Watts, Petri T Kovanen
Approximately 35 million people worldwide suffer from heterozygous familial hypercholesterolaemia (HeFH), a condition characterized by genetically determined life-long elevation of plasma low-density lipoprotein cholesterol (LDL-C). One in three of these patients also inherit an elevated plasma concentration of lipoprotein (a) [Lp(a)], a lipoprotein particle with atherogenic, inflammatory and prothrombotic properties. Accordingly, the combination of high plasma LDL-C and Lp(a) can markedly accelerate premature atherosclerotic cardiovascular disease (ASCVD)...
October 3, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29028546/enzymatic-characterization-and-crystal-structure-analysis-of-chlamydomonas-reinhardtii-dehydroascorbate-reductase-and-their-implications-for-oxidative-stress
#16
Hsin-Yang Chang, Shu-Tseng Lin, Tzu-Ping Ko, Shu-Mei Wu, Tsen-Hung Lin, Yu-Ching Chang, Kai-Fa Huang, Tse-Min Lee
Dehydroascorbate reductase (DHAR) is a key enzyme for glutathione (GSH)-dependent reduction of dehydroascorbate (DHA) to recycled ascorbate (AsA) in plants, and plays a major role against the toxicity of reactive oxygen species (ROS). Previously, we proposed that the increase of AsA regeneration via enhanced DHAR activity modulates the ascorbate-glutathione cycle activity against photooxidative stress in Chlamydomonas reinhardtii. In the present work, we use site-directed mutagenesis and crystal structure analysis to elucidate the molecular basis of how C...
October 3, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29028501/interindividual-variability-in-response-to-continuous-theta-burst-stimulation-in-healthy-adults
#17
Ali Jannati, Gabrielle Block, Lindsay M Oberman, Alexander Rotenberg, Alvaro Pascual-Leone
OBJECTIVE: We used complete-linkage cluster analysis to identify healthy subpopulations with distinct responses to continuous theta-burst stimulation (cTBS). METHODS: 21 healthy adults (age±SD, 36.9±15.2years) underwent cTBS of left motor cortex. Natural log-transformed motor evoked potentials (LnMEPs) at 5-50min post-cTBS (T5-T50) were calculated. RESULTS: Two clusters were found; Group 1 (n=12) that showed significant MEP facilitation at T15, T20, and T50 (p's<0...
September 21, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/29028340/probing-the-binding-pathway-of-braco19-to-a-parallel-stranded-human-telomeric-g-quadruplex-using-molecular-dynamics-binding-simulation-with-amber-dna-ol15-and-ligand-gaff2-force-fields
#18
Babitha Machireddy, Gurmannat Kalra, Subash Chandra Jonnalagadda, Kandalam V Ramanujachary, Chun Wu
Human telomeric DNA G-quadruplex has been identified as a good therapeutic target in cancer treatment. G-quadruplex specific ligands that stabilize the G-quadruplex, have great potential to be developed as anticancer agents. Two crystal structures (an apo form of parallel stranded human telomeric G-quadruplex and its holo form in complex with BRACO19, a potent G-quadruple ligand) have been solved, yet the binding mechanism and pathway remains to be elusive. In this study, we simulated the binding of a free BRACO19 molecule to the apo form of the G-quadruplex using the latest AMBER DNA (OL15) and ligand GAFF2 force field...
October 13, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29025558/glycated-apolipoprotein-a-iv-induces-atherogenesis-in-patients-with-cad-in%C3%A2-type-2-diabetes
#19
Yang Dai, Ying Shen, Qing Run Li, Feng Hua Ding, Xiao Qun Wang, Hong Juan Liu, Xiao Xiang Yan, Ling Jie Wang, Ke Yang, Hai Bo Wang, Qiu Jing Chen, Wei Feng Shen, Rui Yan Zhang, Lin Lu
BACKGROUND: Nonenzymatic glycation of apolipoproteins plays a role in the pathogenesis of the vascular complications of diabetes. OBJECTIVES: This study investigated whether apolipoprotein (apo) A-IV was glycated in patients with type 2 diabetes mellitus (T2DM) and whether apoA-IV glycation was related to coronary artery disease (CAD). The study also determined the biological effects of glycated apoA-IV. METHODS: The authors consecutively enrolled 204 patients with T2DM without CAD (Group I), 515 patients with T2DM with CAD (Group II), and 176 healthy subjects (control group) in this study...
October 17, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29024030/melatonin-prevents-endothelial-cell-pyroptosis-via-regulation-of-long-noncoding-rna-meg3-mir-223-nlrp3-axis
#20
Yong Zhang, Xin Liu, Xue Bai, Yuan Lin, Zhange Li, Jiangbo Fu, Mingqi Li, Tong Zhao, Huan Yang, Ranchen Xu, Jiamin Li, Jin Ju, Benzhi Cai, Chaoqian Xu, Baofeng Yang
Atherosclerosis (AS) is an inflammatory disease linked to endothelial dysfunction. Melatonin is reported to possess substantial anti-inflammatory properties, which has proven to be effective in AS. Emerging literature suggests that pyroptosis plays a critical role during AS progression. However, whether pyroptosis contributes to endothelial dysfunction and the underlying molecular mechanisms remained unexploited. This study was designed to investigate the anti-pyroptotic effects of melatonin in atherosclerotic endothelium and to elucidate the potential mechanisms...
October 11, 2017: Journal of Pineal Research
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