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https://www.readbyqxmd.com/read/28324763/interaction-of-apoe-e4-and-poor-glycemic-control-predicts-white-matter-hyperintensity-growth-from-73-to-76
#1
Simon R Cox, Stuart J Ritchie, David Alexander Dickie, Alison Pattie, Natalie A Royle, Janie Corley, Benjamin S Aribisala, Sarah E Harris, Maria Valdés Hernández, Alan J Gow, Susana Muñoz Maniega, John M Starr, Mark E Bastin, Joanna M Wardlaw, Ian J Deary
We examined whether apolipoprotein E (APOE) status interacts with vascular risk factors (VRFs) to predict the progression of white matter hyperintensities (WMHs) on brain MRI scans over a specific period of life in older age when the risk of dementia increases. At age 73 years, baseline VRFs were assessed via self-reported history of diabetes, hypertension, smoking, and hypercholesterolemia, and via objective measures of blood HbA1c, body mass index, diastolic and systolic blood pressure, and blood high-density lipoprotein to total cholesterol (HDL) ratio...
February 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28324341/beta-amyloid-deposition-in-patients-with-major-depressive-disorder-with-differing-levels-of-treatment-resistance-a-pilot-study
#2
Peng Li, Ing-Tsung Hsiao, Chia-Yih Liu, Chia-Hsiang Chen, She-Yao Huang, Tzu-Chen Yen, Kuan-Yi Wu, Kun-Ju Lin
BACKGROUND: Lack of treatment response in patients with late-life depression is common. The role of brain beta-amyloid (Aβ) deposition in treatment outcome in subjects with late-life depression remains unclear. The present study aimed to investigate brain Aβ deposition in patients with major depressive disorder (MDD) with differing treatment outcomes in vivo using (18)F-florbetapir imaging. This study included 62 MDD patients and 18 healthy control subjects (HCs).We first employed the Maudsley staging method (MSM) to categorize MDD patients into two groups according to treatment response: mild treatment resistance (n = 29) and moderate-to-severe treatment resistance (n = 33)...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28323832/age-related-cognitive-decline-and-associations-with-sex-education-and-apolipoprotein-e-genotype-across-ethnocultural-groups-and-geographic-regions-a-collaborative-cohort-study
#3
Darren M Lipnicki, John D Crawford, Rajib Dutta, Anbupalam Thalamuthu, Nicole A Kochan, Gavin Andrews, M Fernanda Lima-Costa, Erico Castro-Costa, Carol Brayne, Fiona E Matthews, Blossom C M Stephan, Richard B Lipton, Mindy J Katz, Karen Ritchie, Jacqueline Scali, Marie-Laure Ancelin, Nikolaos Scarmeas, Mary Yannakoulia, Efthimios Dardiotis, Linda C W Lam, Candy H Y Wong, Ada W T Fung, Antonio Guaita, Roberta Vaccaro, Annalisa Davin, Ki Woong Kim, Ji Won Han, Tae Hui Kim, Kaarin J Anstey, Nicolas Cherbuin, Peter Butterworth, Marcia Scazufca, Shuzo Kumagai, Sanmei Chen, Kenji Narazaki, Tze Pin Ng, Qi Gao, Simone Reppermund, Henry Brodaty, Antonio Lobo, Raúl Lopez-Anton, Javier Santabárbara, Perminder S Sachdev
BACKGROUND: The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. METHODS AND FINDINGS: We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54-105 y (42% male), including 3...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28323831/genetic-assessment-of-age-associated-alzheimer-disease-risk-development-and-validation-of-a-polygenic-hazard-score
#4
Rahul S Desikan, Chun Chieh Fan, Yunpeng Wang, Andrew J Schork, Howard J Cabral, L Adrienne Cupples, Wesley K Thompson, Lilah Besser, Walter A Kukull, Dominic Holland, Chi-Hua Chen, James B Brewer, David S Karow, Karolina Kauppi, Aree Witoelar, Celeste M Karch, Luke W Bonham, Jennifer S Yokoyama, Howard J Rosen, Bruce L Miller, William P Dillon, David M Wilson, Christopher P Hess, Margaret Pericak-Vance, Jonathan L Haines, Lindsay A Farrer, Richard Mayeux, John Hardy, Alison M Goate, Bradley T Hyman, Gerard D Schellenberg, Linda K McEvoy, Ole A Andreassen, Anders M Dale
BACKGROUND: Identifying individuals at risk for developing Alzheimer disease (AD) is of utmost importance. Although genetic studies have identified AD-associated SNPs in APOE and other genes, genetic information has not been integrated into an epidemiological framework for risk prediction. METHODS AND FINDINGS: Using genotype data from 17,008 AD cases and 37,154 controls from the International Genomics of Alzheimer's Project (IGAP Stage 1), we identified AD-associated SNPs (at p < 10-5)...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28323826/apoe-related-risk-of-mild-cognitive-impairment-and-dementia-for-prevention-trials-an-analysis-of-four-cohorts
#5
Jing Qian, Frank J Wolters, Alexa Beiser, Mary Haan, M Arfan Ikram, Jason Karlawish, Jessica B Langbaum, John M Neuhaus, Eric M Reiman, J Scott Roberts, Sudha Seshadri, Pierre N Tariot, Beth McCarty Woods, Rebecca A Betensky, Deborah Blacker
BACKGROUND: With the onset of prevention trials for individuals at high risk for Alzheimer disease, there is increasing need for accurate risk prediction to inform study design and enrollment, but available risk estimates are limited. We developed risk estimates for the incidence of mild cognitive impairment (MCI) or dementia among cognitively unimpaired individuals by APOE-e4 dose for the genetic disclosure process of the Alzheimer's Prevention Initiative Generation Study, a prevention trial in cognitively unimpaired APOE-e4/e4 homozygote individuals...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28323660/impact-of-rare-variants-in-autosomal-dominant-hypercholesterolemia-causing-genes
#6
Sebastiano Calandra, Patrizia Tarugi, Stefano Bertolini
PURPOSE OF REVIEW: The systematic analysis of the major candidate genes in autosomal dominant hypercholesterolemia (ADH) and the use of next-generation sequencing (NGS) technology have made possible the discovery of several rare gene variants whose pathogenic effect in most cases remains poorly defined. RECENT FINDINGS: One major advance in the field has been the adoption of a set of international guidelines for the assignment of pathogenicity to low-density lipoprotein receptor (LDLR) gene variants based on the use of softwares, complemented with data available from literature and public databases...
March 18, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28319835/convergent-and-divergent-effects-of-apolipoprotein-e-%C3%AE%C2%B54-and-%C3%AE%C2%B52-alleles-on-amygdala-functional-networks-in-nondemented-older-adults
#7
Liang Gong, Hao Shu, Cancan He, Qing Ye, Feng Bai, Chunming Xie, Zhijun Zhang
Traditionally, in the context of Alzheimer's disease, the apolipoprotein E ε2 (APOEε2) allele is a protective factor and the APOEε4 allele is a destructive factor. However, this inverse relationship has recently been challenged, and the neural mechanisms underlying the effects of APOE genotype on Alzheimer's disease remain unclear. A resting-state functional magnetic resonance imaging study was conducted to investigate the effects of APOE genotype and age on amygdala functional connectivity (AFC) networks in 84 patients with amnestic mild cognitive impairment and 124 cognitively normal order adults...
February 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28319394/a-network-of-conformational-transitions-in-the-apo-form-of-ndm-1-enzyme-revealed-by-md-simulation-and-a-markov-state-model
#8
Kaifu Gao, Yunjie Zhao
New Delhi metallo-β-lactamase-1 (NDM-1) is a novel β-Lactamase enzyme that confers enteric bacteria with nearly complete resistance to all β-lactam antibiotics, so raises a formidable and global threat to human health. However, the binding mechanism between apo-NDM-1 and antibiotics as well as related conformational changes remains poorly understood, which largely hinders the overcoming of its antibiotic resistance. In our study, long-time conventional molecular dynamics simulation and Markov state models were applied to reveal both dynamical and conformational landscape of apo-NDM-1: the MD simulation demonstrates that the loop L3, which is responsible for antibiotic binding, is the most flexible and undergoes dramatic conformational changes; moreover, the Markov state model built from the simulation maps four metastable states including open, semi-open and closed conformations of the loop L3 as well as frequent transitions between the states...
March 20, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28319241/alzheimer-disease-signature-neurodegeneration-and-apoe-genotype-in-mild-cognitive-impairment-with-suspected-non-alzheimer-disease-pathophysiology
#9
Stefanie Schreiber, Frank Schreiber, Samuel N Lockhart, Andy Horng, Alexandre Bejanin, Susan M Landau, William J Jagust
Importance: There are conflicting results claiming that Alzheimer disease signature neurodegeneration may be more, less, or similarly advanced in individuals with β-amyloid peptide (Aβ)-negative (Aβ-) suspected non-Alzheimer disease pathophysiology (SNAP) than in Aβ-positive (Aβ+) counterparts. Objective: To examine patterns of neurodegeneration in individuals with SNAP compared with their Aβ+ counterparts. Design, Setting, and Participants: A longitudinal cohort study was conducted among individuals with mild cognitive impairment (MCI) and cognitively normal individuals receiving care at Alzheimer's Disease Neuroimaging Initiative sites in the United States and Canada for a mean follow-up period of 30...
March 20, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28319084/structural-and-mechanistic-insights-into-an-archaeal-dna-guided-argonaute-protein
#10
Sarah Willkomm, Christine A Oellig, Adrian Zander, Tobias Restle, Ronan Keegan, Dina Grohmann, Sabine Schneider
Argonaute (Ago) proteins in eukaryotes are known as key players in post-transcriptional gene silencing(1), while recent studies on prokaryotic Agos hint at their role in the protection against invading DNA(2,3). Here, we present crystal structures of the apo enzyme and a binary Ago-guide complex of the archaeal Methanocaldococcus jannaschii (Mj) Ago. Binding of a guide DNA leads to large structural rearrangements. This includes the structural transformation of a hinge region containing a switch helix, which has been shown for human Ago2 to be critical for the dynamic target search process(4-6)...
March 20, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28319083/structures-of-human-o-glcnacase-and-its-complexes-reveal-a-new-substrate-recognition-mode
#11
Baobin Li, Hao Li, Lei Lu, Jiaoyang Jiang
Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft...
March 20, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28317295/two-year-follow-up-of-patients-with-septic-shock-presenting-with-low-hdl-the-effect-upon-acute-kidney-injury-death-and-estimated-glomerular-filtration-rate
#12
K Roveran Genga, C Lo, M Cirstea, G Zhou, K R Walley, J A Russell, A Levin, J H Boyd
BACKGROUND: Sepsis is associated with decreased levels of high-density lipoprotein (HDL) cholesterol. HDL has anti-inflammatory properties, and the use of Apo A-I mimetic peptides is associated with renal function improvement in animal models of sepsis. However, it is not known whether decreased HDL level results in impaired renal function in human sepsis. We investigated whether low levels of HDL conferred an increased risk of sepsis-associated acute kidney injury (AKI) or long-term decreased estimated glomerular filtration rate (eGFR) after sepsis...
March 19, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28315714/cadmium-induced-malignant-transformation-of-rat-liver-cells-potential-key-role-and-regulatory-mechanism-of-altered-apolipoprotein-e-expression-in-enhanced-invasiveness
#13
Masayo Suzuki, Shuso Takeda, Noriko Teraoka-Nishitani, Akane Yamagata, Takahiro Tanaka, Marika Sasaki, Natsuki Yasuda, Makiko Oda, Tatsuji Okano, Kazuhiro Yamahira, Yuta Nakamura, Takanobu Kobayashi, Katsuhito Kino, Hiroshi Miyazawa, Michael P Waalkes, Masufumi Takiguchi
Cadmium is a transition metal that is classified as human carcinogen by the International Agency for Research on Cancer (IARC) with multiple target sites. Many studies using various model systems provide evidence of cadmium-induced malignancy formation in vivo or malignant cell transformation in vitro. Nonetheless, further studies are needed to completely understand the mechanisms of cadmium carcinogenicity. Our prior studies have utilized a rat liver epithelial cell line (TRL 1215) as a model for cadmium-induced malignant transformation...
March 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28315324/nucleolin-protects-macrophages-from-oxldl-induced-foam-cell-formation-through-up-regulating-abca1-expression
#14
Yuanbin Li, Bimei Jiang, Pengfei Liang, Zhongyi Tong, Meidong Liu, Qinglan Lv, Yanjuan Liu, Xuanyou Liu, Yuting Tang, Xianzhong Xiao
Our recent studies have indicated that nucleolin, as a multifunctional RNA-binding protein, exerts protective effects in the myocardial cells and endothelial cells under the condition of oxidative stress. However, the function of nucleolin and its potential mechanism in macrophage-derived foam cell formation remain largely unexplored. ApoE-/- mice were fed with a high-fat diet (HFD) for 10-24 weeks. Protein expression was measured by western blotting or immunofluorescence, and gene expression at the mRNA level was detected by qRT-PCR...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28314859/effects-of-cetp-inhibition-with-anacetrapib-on-metabolism-of-vldl-tg-and-plasma-apolipoproteins-c-ii-c-iii-and-e
#15
John S Millar, Michael E Lassman, Tiffany Thomas, Rajasekhar Ramakrishnan, Patricia Jumes, Richard L Dunbar, Emile M deGoma, Amanda L Baer, Wahida Karmally, Daniel S Donovan, Hashmi Rafeek, John A Wagner, Stephen Holleran, Joseph Obunike, Yang Liu, Soumia Aoujil, Taylor Standiford, David E Gutstein, Henry N Ginsberg, Daniel J Rader, Gissette Reyes-Soffer
Cholesteryl ester transfer protein (CETP) mediates the transfer of HDL cholesteryl esters(CE) for TG in VLDL/LDL. CETP inhibition, with anacetrapib, increases HDL-cholesterol(C), reduces LDL-C and lowers TG levels. This study describes the mechanisms responsible for TG lowering by examining the kinetics of VLDL-TG and apolipoproteins (apo) C-II, C-III, and E. Hypercholesterolemic subjects were randomized to either placebo(N=10) or atorvastatin 20 mg/qd(N=29) for 4 weeks(period 1) followed by 8-weeks of anacetrapib, 100 mg/qd(period 2)...
March 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28304324/assessment-of-serum-apolipoprotien-b-and-apolipoprotein-a-1-and-their-ratio-in-healthy-full-term-small-for-gestational-age-newborns
#16
A Agrawal, J Shrivastava, R Dwivedi, M Siddiqui
BACKGROUND: Programmed changes in growth restricted fetuses can increase the risk of adulthood diseases due to elevated serum cholesterol and apolipoprotein-B (Apo-B) concentrations. Increasing evidence demonstrated the role of apoB/apoA-I ratio as a strong risk factor for cardiovascular diseases. OBJECTIVE: To determine the concentration of cord blood lipoproteins and apolipoproteins as well as their correlation with birth weight. METHODS: This cross-sectional study was conducted in a teaching institution of central India...
March 16, 2017: Journal of Neonatal-perinatal Medicine
https://www.readbyqxmd.com/read/28304310/smoking-apoe-genotype-and-cognitive-decline-the-rotterdam-study
#17
Robin Wingbermühle, Ke-Xin Wen, Frank Wolters, M Arfan Ikram, Daniel Bos
The association of smoking with preclinical cognitive decline remains unclear and may be modified by the APOEɛ4 genotype. In 5,705 participants (mean age: 63.9±9.1 years; 57.4% women) from the population-based Rotterdam Study, we investigated the relationship between smoking and cognitive decline over a 5.5-year period and examined potential effect modification by APOEɛ4 genotype. We found that current smoking was related to decline in global cognition [difference compared to never smoking: -0.06 (95% C...
March 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28304301/modeling-the-relationships-among-late-life-body-mass-index-cerebrovascular-disease-and-alzheimer-s-disease-neuropathology-in-an-autopsy-sample-of-1-421-subjects-from-the-national-alzheimer-s-coordinating-center-data-set
#18
Michael L Alosco, Jonathan Duskin, Lilah M Besser, Brett Martin, Christine E Chaisson, John Gunstad, Neil W Kowall, Ann C McKee, Robert A Stern, Yorghos Tripodis
The relationship between late-life body mass index (BMI) and Alzheimer's disease (AD) is poorly understood due to the lack of research in samples with autopsy-confirmed AD neuropathology (ADNP). The role of cerebrovascular disease (CVD) in the interplay between late-life BMI and ADNP is unclear. We conducted a retrospective longitudinal investigation and used joint modeling of linear mixed effects to investigate causal relationships among repeated antemortem BMI measurements, CVD (quantified neuropathologically), and ADNP in an autopsy sample of subjects across the AD clinical continuum...
March 13, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28302649/endothelial-protective-monocyte-patrolling-in-large-arteries-intensified-by-western-diet-and-atherosclerosis
#19
Amado Quintar, Sara McArdle, Dennis Wolf, Alex Marki, Erik Ehinger, Melanie Vassallo, Jacqueline F Miller, Zbigniew Mikulski, Klaus Ley, Konrad Buscher
Rationale: Non-classical mouse monocyte (CX3CR1(high), Ly-6C(low)) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Due to technical challenges it is currently not established how patrolling occurs in large arteries. Objective: This study was undertaken to elucidate the molecular, migratory and functional phenotype of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic and atherosclerotic conditions...
March 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28301848/predictors-of-reversion-from-mild-cognitive-impairment-to-normal-cognition
#20
Seema Y Pandya, Laura H Lacritz, Myron F Weiner, Martin Deschner, Fu L Woon
BACKGROUND/AIMS: Few studies have examined predictors of reversion from mild cognitive impairment (MCI) to normal cognition. We sought to identify baseline predictors of reversion, using the National Alzheimer's Coordinating Center Uniform Data Set, by comparing MCI individuals who reverted to normal cognition to those who progressed to dementia. METHODS: Participants (n = 1,208) meeting MCI criteria were evaluated at the baseline visit and 3 subsequent annual visits...
March 17, 2017: Dementia and Geriatric Cognitive Disorders
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