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APOE Gene

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https://www.readbyqxmd.com/read/28634213/omega-3-fatty-acids-increase-the-unfolded-protein-response-and-improve-amyloid-%C3%AE-phagocytosis-by-macrophages-of-patients-with-mild-cognitive-impairment
#1
Henry M Olivera-Perez, Larry Lam, Johnny Dang, Weilan Jiang, Fabian Rodriguez, Elizabeth Rigali, Sarah Weitzman, Verna Porter, Liudmilla Rubi, Marco Morselli, Matteo Pellegrini, Milan Fiala
Mϕs of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ. ω-3 in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI. Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1...
June 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28632940/characterization-of-the-i4399m-variant-of-apolipoprotein-a-implications-for-altered-prothrombotic-properties-of-lipoprotein-a
#2
Corey A Scipione, Jackson T McAiney, Daniel J Simard, Zainab A Bazzi, Matthew Gemin, Rocco Romagnuolo, Fraser L Macrae, Robert A Ariëns, Robert A Hegele, Janeen Auld, James W Gauld, Michael B Boffa, Marlys L Koschinsky
BACKGROUND: Lipoprotein(a) (Lp(a)) is a causal risk factor for a variety of cardiovascular diseases. Apolipoprotein(a) (apo(a)), the distinguishing component of Lp(a), is homologous to plasminogen, suggesting that Lp(a) can interfere with the normal fibrinolytic functions of plasminogen. This has implications for the persistence of fibrin clots in the vasculature and hence to atherothrombotic diseases. A single nucleotide polymorphism (rs3798220) in the gene encoding apo(a) has been reported that results in an Ile to Met substitution in the protease-like domain (I4399M variant)...
June 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28631352/overexpressing-stamp2-attenuates-adipose-tissue-angiogenesis-and-insulin-resistance-in-diabetic-apoe-ldlr-mouse-via-a-ppar%C3%AE-cd36-pathway
#3
Feng Wang, Lu Han, Ran-Ran Qin, Yao-Yuan Zhang, Di Wang, Zhi-Hao Wang, Meng-Xiong Tang, Yun Zhang, Ming Zhong, Wei Zhang
The aim of this study was to investigate whether overexpression of STAMP2 improves insulin resistance by regulating angiogenesis in adipose tissues. The characteristics of diabetic mice were measured by serial metabolite and pathology tests. Samples were obtained from epididymal, subcutaneous and brown adipose tissues. Histological and morphological analysis demonstrated that STAMP2 gene overexpression reduced adipocyte size, angiogenesis in epididymal and brown adipose tissues. On aortic ring assay, microvessels sprouting from aortas were significantly inhibited after STAMP2 gene overexpression...
June 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28626864/detecting-genetic-association-through-shortest-paths-in-a-bidirected-graph
#4
Masao Ueki, Yoshinori Kawasaki, Gen Tamiya
Genome-wide association studies (GWASs) commonly use marginal association tests for each single-nucleotide polymorphism (SNP). Because these tests treat SNPs as independent, their power will be suboptimal for detecting SNPs hidden by linkage disequilibrium (LD). One way to improve power is to use a multiple regression model. However, the large number of SNPs preclude simultaneous fitting with multiple regression, and subset regression is infeasible because of an exorbitant number of candidate subsets. We therefore propose a new method for detecting hidden SNPs having significant yet weak marginal association in a multiple regression model...
June 19, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28623948/one-carbon-metabolism-cognitive-impairment-and-csf-measures-of-alzheimer-pathology-homocysteine-and-beyond
#5
Loïc Dayon, Seu Ping Guiraud, John Corthésy, Laeticia Da Silva, Eugenia Migliavacca, Domilė Tautvydaitė, Aikaterini Oikonomidi, Barbara Moullet, Hugues Henry, Sylviane Métairon, Julien Marquis, Patrick Descombes, Sebastiano Collino, François-Pierre J Martin, Ivan Montoliu, Martin Kussmann, Jérôme Wojcik, Gene L Bowman, Julius Popp
BACKGROUND: Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults...
June 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28617356/-the-association-of-the-fas-apo-1-rs2234767-gene-polymorphism-with-the-risk-and-rapid-progression-of-multiple-sclerosis
#6
O M Nochevnaya, O V Pereverzeva, E A Sokolova, M L Phillipenko, S V Zamyatina, A S Palaschenko, E S Zhdanova, S A Elchaninova, I V Smagina
AIM: To evaluate the association of the FAS/APO-1 (rs2234767) gene polymorphism with the risk of multiple sclerosis and its progression dynamics. MATERIAL AND METHODS: A case-control study included 100 patients with recurrent multiple sclerosis (MS), Russians from the Altai Territory, and 100 healthy volunteers. Real-time polymerase chain reaction was used to genotype the 1377G>A polymorphism in the promoter of the FAS/APO-1 (rs2234767) gene. Association of this polymorphism with the risk of multiple sclerosis and its progression was evaluated...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28612427/simulation-based-investigation-of-deleterious-nssnp-s-in-atxn2-gene-and-its-structural-consequence-towards-spinocerebellar-ataxia
#7
Siddharth Sinha, Sharad Verma, Aditi Singh, Pallavi Somvanshi, Abhinav Grover
Spinocerebellar degeneration, termed as ataxia is a neurological disorder of central nervous system, characterized by limb in-coordination and a progressive gait. The patient also demonstrates specific symptoms of muscle weakness, slurring of speech, and decreased vibration senses. Expansion of polyglutamine trinucleotide (CAG) within ATXN2 gene with 35 or more repeats, results in spinocerebellar ataxia type-2. Protein ataxin-2 coded by ATXN2 gene has been reported to have a crucial role in translation of the genetic information through sequestering the histone acetyl transferases (HAT) resulting in a state of hypo-acetylation...
June 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28612048/obesity-accelerates-alzheimer-related-pathology-in-apoe4-but-not-apoe3-mice
#8
V Alexandra Moser, Christian J Pike
Alzheimer's disease (AD) risk is modified by both genetic and environmental risk factors, which are believed to interact to cooperatively modify pathogenesis. Although numerous genetic and environmental risk factors for AD have been identified, relatively little is known about potential gene-environment interactions in regulating disease risk. The strongest genetic risk factor for late-onset AD is the ε4 allele of apolipoprotein E (APOE4). An important modifiable risk factor for AD is obesity, which has been shown to increase AD risk in humans and accelerate development of AD-related pathology in rodent models...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28607446/apoe-gene-polymorphism-in-long-lived-individuals-from-a-central-china-population
#9
Guodong Liu, Xiang Liu, Pulin Yu, Qi Wang, Hua Wang, Chenfang Li, Guangming Ye, Xiaoling Wu, Chunling Tan
Previous studies from European and East Asian cohorts reported conflicting results over whether and how the frequencies of the three common alleles, ε2, ε3 and ε4, of the apolioprotein E gene (APOE), in long-lived individuals differ from those in younger age groups. This study was the first to analyse these frequencies of long-lived individuals from central China. Genotyping of APOE alleles and genotypes was carried out in 70 long-lived individuals and 204 younger controls. No difference in the frequency of any APOE allele or genotype was found between the long-lived participants and their younger controls, but the long-lived group seemed to have a higher ε4 frequency (15...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607149/polycomb-repressive-complex-2-in-an-autoinhibited-state
#10
Matthew Bratkowski, Xin Yang, Xin Liu
Polycomb-group proteins control many fundamental biological processes, such as anatomical development in mammals and vernalization in plants. Polycomb repressive complex 2 (PRC2) is responsible for methylation of histone H3 lysine 27 (H3K27), and trimethylated H3K27 (H3K27me3) is implicated in epigenetic gene silencing. Recent genomic, biochemical, and structural data indicate that PRC2 is broadly conserved from yeast to human in many aspects. Here, we determined the crystal structure of an apo PRC2 from the fungus Chaetomium thermophilum captured in a bona fide autoinhibited state, which represents a novel conformation of PRC2 associated with enzyme regulation in light of the basal and stimulated states that we reported previously...
June 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28605058/cardiovascular-pharmacogenomics-and-cognitive-function-in-patients-with-schizophrenia
#11
Kristen M Ward, A Zarina Kraal, Stephanie A Flowers, Vicki L Ellingrod
STUDY OBJECTIVE: To examine the impact of multiple risk alleles for cognitive dysfunction and cardiovascular disease risk on cognitive function, and to determine if these relationships varied by cognitive reserve (CR) or concomitant medication use in patients with schizophrenia. DESIGN: Cross-sectional study. SETTING: Ambulatory mental health centers. PATIENTS: A total of 122 adults with a schizophrenia spectrum diagnosis who were maintained on a stable antipsychotic regimen for at least 6 months prior to study enrollment; patients were divided into three CR groups based on years of formal education: no high school completion or equivalent (low-education group [18 patients]); completion of high school or equivalent (moderate-education group [36 patients]; or any degree of post-high school education (high-education group [68 patients])...
June 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28601639/tofacitinib-ameliorates-atherosclerosis-and-reduces-foam-cell-formation-in-apoe-deficient-mice
#12
Zaicun Wang, Shumei Wang, Zunzhe Wang, Tiantian Yun, Chenchen Wang, Huating Wang
Atherosclerosis is a chronic inflammatory cardiovascular disease with high mortality worldwide. Tofacitinib (CP-690,550), an oral small-molecule Janus kinase inhibitor, has been shown to be effective in the treatment of rheumatoid arthritis, autoimmune encephalomyelitis and ulcerative colitis. However, its protective effect against atherosclerosis remains poorly understood. The aim of the present study was to evaluate the effects of Tofacitinib on atherogenic diet (ATD)-induced atherosclerosis using apolipoprotein E deficient (apoE-/-) mice...
June 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28600950/histamine-promotes-the-differentiation-of-macrophages-from-cd11b-myeloid-cells-and-formation-of-foam-cells-through-a-stat6-dependent-pathway
#13
Lili Xu, Dengfeng Cheng, Zheyong Huang, Suling Ding, Weiwei Zhang, Hui Tan, Hongcheng Shi, Ruizhen Chen, Yunzeng Zou, Timothy C Wang, Xiangdong Yang, Junbo Ge
BACKGROUND AND AIMS: The enzyme histidine decarboxylase (Hdc), which generates histamine, is highly expressed in CD11b(+)Gr-1(+) myeloid cells that play a critical role in infection, inflammation and tumorigenesis. The aim of this study was to explore the role of Hdc-expressing CD11b(+) myeloid cells or histamine in atherogenesis. METHODS: Hdc-EGFP bacterial artificial chromosome (BAC) transgenic reporter mice (Hdc-EGFP) were used to track Hdc expression during the development of atherosclerosis...
May 23, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28596117/disrupted-white-matter-structural-networks-in-healthy-older-adults-apoe-%C3%AE%C2%B54-carriers-an-international-multicenter-dti-study
#14
Enrica Cavedo, Simone Lista, Katrine Rojkova, Patrizia Andrea Chiesa, Marion Houot, Katharina Brueggen, Janusch Blautzik, Arun L W Bokde, Bruno Dubois, Frederik Barkhof, Petra J W Pouwels, Stefan Teipel, Harald Hampel
The ε4 allelic variant of the Apolipoprotein E gene (APOE ε4) is the best-established genetic risk factor for late-onset Alzheimer's disease (AD). White matter (WM) microstructural damages measured with Diffusion Tensor Imaging (DTI) represent an early sign of fiber tract disconnection in AD. We examined the impact of APOEε4 on WM microstructure in elderly individuals from the multicenter European DTI Study on Dementia. Voxelwise statistical analysis of Fractional anisotropy (FA), mean diffusivity, radial and axial diffusivity (MD, radD and axD respectively) was carried out using Tract-Based Spatial Statistics...
June 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28595908/association-of-angiotensin-ii-receptor-1-and-lectin-like-oxidized-low-density-lipoprotein-receptor-1-mediates-the-cardiac-hypertrophy%C3%A2-induced-by-oxidized-low-density-lipoprotein
#15
Yunzi Zhao, Yuqiu Li, Xiaohui Ning, Keping Chen, Shu Zhang
To date the molecular mechanism of cardiac hypertrophy has not been completely elucidated. Since oxidized low-density lipoprotein (ox-LDL) is considered a risk marker for early ventricular remodeling, we speculated that ox-LDL may be related to cardiac hypertrophy. We observed the significantly upregulation of plasma ox-LDL and hypertrophic responses, such as cardiomyocyte size and specific gene expressions in Apo E(-/-) mice fed with high fat diet, accompanied by the upregulation of AT1-R and lectin-like oxidized low-density protein receptor 1 (LOX-1)...
June 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28592707/endothelial-nitric-oxide-synthase-independent-pleiotropic-effects-of-pitavastatin-against-atherogenesis-and-limb-ischemia-in-mice
#16
Takeshi Mitsuhashi, Ryoko Uemoto, Kazue Ishikawa, Sumiko Yoshida, Yasumasa Ikeda, Shusuke Yagi, Toshio Matsumoto, Masashi Akaike, Ken-Ichi Aihara
AIM: Statins have a protective impact against cardiovascular diseases through not only lipid-lowering effects but also pleiotropic effects, including activation of the endothelial nitric oxide synthase (eNOS) system. We aimed to clarify the protective effects of a statin against atherogenesis and ischemia in eNOS(-/-) mice. METHODS: Study 1. eNOS(-/-) Apolipoprotein E (ApoE)(-/-) mice were treated with a vehicle or pitavastatin (0.3 mg/kg/day) for 4 weeks...
June 6, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28589856/association-analysis-of-rare-variants-near-the-apoe-region-with-csf-and-neuroimaging-biomarkers-of-alzheimer-s-disease
#17
Kwangsik Nho, Sungeun Kim, Emrin Horgusluoglu, Shannon L Risacher, Li Shen, Dokyoon Kim, Seunggeun Lee, Tatiana Foroud, Leslie M Shaw, John Q Trojanowski, Paul S Aisen, Ronald C Petersen, Clifford R Jack, Michael W Weiner, Robert C Green, Arthur W Toga, Andrew J Saykin
BACKGROUND: The APOE ε4 allele is the most significant common genetic risk factor for late-onset Alzheimer's disease (LOAD). The region surrounding APOE on chromosome 19 has also shown consistent association with LOAD. However, no common variants in the region remain significant after adjusting for APOE genotype. We report a rare variant association analysis of genes in the vicinity of APOE with cerebrospinal fluid (CSF) and neuroimaging biomarkers of LOAD. METHODS: Whole genome sequencing (WGS) was performed on 817 blood DNA samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI)...
May 24, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28578430/expression-profiles-of-cholesterol-metabolism-related-genes-are-altered-during-development-of-experimental-autoimmune-encephalomyelitis-in-the-rat-spinal-cord
#18
Irena Lavrnja, Kosara Smiljanic, Danijela Savic, Aleksandra Mladenovic-Djordjevic, Katarina Tesovic, Selma Kanazir, Sanja Pekovic
Increased evidence suggests that dysregulation of cholesterol metabolism may be a key event contributing to progression of multiple sclerosis (MS). Using an experimental autoimmune encephalomyelitis (EAE) model of MS we revealed specific changes in the mRNA and protein expression of key molecules involved in the maintaining of cholesterol homeostasis in the rat spinal cord: 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46A1) during the course of disease...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28577227/-search-for-risk-genes-in-alzheimer-s-disease
#19
REVIEW
I Karaca, H Wagner, A Ramirez
Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. The susceptibility to AD is determined by a complex interaction between genetic, epigenetic, and environmental factors. Herein, the risk that can be attributed to genetic factors is high (up to 80%). While most AD patients are sporadic, in rare families Mendelian mode of inheritance can be observed. In these rare familial cases, full penetrant mutations have been identified in APP, PSEN1, and PSEN2. Mutations in these three genes are however rarely found in sporadic AD...
June 2, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28577205/a-preliminary-study-ps1-increases-u1-snrna-expression-associated-with-ad
#20
Zhi Cheng, Zhanqiang Du, Yingchun Shang, Yuling Zhang, Tao Zhang
U1 small nuclear RNA (snRNA) is selectively enriched in 100% of familial Alzheimer's disease (AD) resulting from presenilin1 (PS1) and amyloid precursor protein (APP) mutations. However, it remains unknown what gene or protein cause the U1 snRNA overexpression and then resulted in AD. Using SH-SY5Y cells, we discovered that PS1 induced the overexpression of U1 snRNA, which increased the production of Aβ. Moreover, the U1 snRNA overexpression induced the upregulation of apoe and clu transcripts. In addition, the levels of phosphorylation of tau protein at Thr212 were significantly elevated in U1 snRNA overexpression cells...
June 3, 2017: Journal of Molecular Neuroscience: MN
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