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https://www.readbyqxmd.com/read/29051098/impact-of-tyrosine-nitration-at-positions-tyr307-and-tyr335-on-structural-dynamics-of-lipoprotein-associated-phospholipase-a2-a-therapeutically-important-cardiovascular-biomarker-for-atherosclerosis
#1
Arun Bahadur Gurung, Atanu Bhattacharjee
Protein tyrosine nitration (PTN) is a post translational event which results in the generation of 3-Nitrotyrosine (3-NT). High levels of 3-NT were reported in several human diseases such as Parkinson's disease, Alzheimer's disease, amylotrophic lateral sclerosis and coronary artery disease. It was reported that PTN at positions 307 and 335 of Lipoprotein-associated phospholipase A2 (Lp-PLA2) curtails its enzymatic activity but the mechanism of inhibition at the structure level is still incomprehensible. The present study is an in silico endeavor to understand nitrative stress induced structural changes in Lp-PLA2...
October 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29025764/higher-risk-of-vascular-dementia-in-myocardial-infarction-survivors
#2
Jens Sundbøll, Erzsébet Hováth-Puhó, Kasper Adelborg, Morten Schmidt, Lars Pedersen, Hans Erik Bøtker, Victor W Henderson, Henrik T Sørensen
Background -Increased risk of dementia after myocardial infarction (MI) may be mediated by shared risk factors (e.g., atherosclerosis) and post-MI stroke. We examined risk of dementia in 1-year survivors of MI. Methods -Using Danish medical registries, we conducted a nationwide population-based cohort study of all patients with first-time MI and a sex-, birth year-, and calendar year-matched general population comparison cohort without MI (1980-2012). Cox regression analysis was used to compute 1-35 year adjusted hazard ratios (aHRs) for dementia, controlled for matching factors and adjusted for comorbidities and socioeconomic status...
October 12, 2017: Circulation
https://www.readbyqxmd.com/read/29018129/neuroimaging-correlates-of-cerebral-microbleeds-the-aric-study-atherosclerosis-risk-in-communities
#3
Jonathan Graff-Radford, Jeannette Simino, Kejal Kantarci, Thomas H Mosley, Michael E Griswold, B Gwen Windham, A Richey Sharrett, Marilyn S Albert, Rebecca F Gottesman, Clifford R Jack, Prashanthi Vemuri, David S Knopman
BACKGROUND AND PURPOSE: Cerebral microbleed (CMB) location (deep versus strictly lobar) may elucidate underlying pathology with deep CMBs being more associated with hypertensive vascular disease and lobar CMBs being more associated with cerebral amyloid angiopathy. The objective of this study was to determine whether neuroimaging signs of vascular disease and Alzheimer pathology are associated with different types of CMBs. METHODS: Among 1677 nondemented ARIC (Atherosclerosis Risk in Communities) participants (mean age=76±5 years; 40% men; 26% black) with 3-Tesla MRI scans at the fifth examination (2011-2013), we fit multinomial logistic regression models to quantify relationships of brain volumes (Alzheimer disease signature regions, total gray matter, frontal gray matter, and white matter hyperintensity volumes), infarct frequencies (lacunar, nonlacunar, and total), and apolipoprotein E(number of ε4 alleles) with CMB location (none, deep/mixed, or strictly lobar CMBs)...
October 10, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28943355/boron-based-inhibitors-of-the-nlrp3-inflammasome
#4
Alex G Baldwin, Jack Rivers-Auty, Michael J D Daniels, Claire S White, Carl H Schwalbe, Tom Schilling, Halah Hammadi, Panichakorn Jaiyong, Nicholas G Spencer, Hazel England, Nadia M Luheshi, Manikandan Kadirvel, Catherine B Lawrence, Nancy J Rothwell, Michael K Harte, Richard A Bryce, Stuart M Allan, Claudia Eder, Sally Freeman, David Brough
NLRP3 is a receptor important for host responses to infection, yet is also known to contribute to devastating diseases such as Alzheimer's disease, diabetes, atherosclerosis, and others, making inhibitors for NLRP3 sought after. One of the inhibitors currently in use is 2-aminoethoxy diphenylborinate (2APB). Unfortunately, in addition to inhibiting NLRP3, 2APB also displays non-selective effects on cellular Ca(2+) homeostasis. Here, we use 2APB as a chemical scaffold to build a series of inhibitors, the NBC series, which inhibit the NLRP3 inflammasome in vitro and in vivo without affecting Ca(2+) homeostasis...
September 1, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28941727/intravenous-treatment-with-human-recombinant-apoa-i-milano-reduces-beta-amyloid-cerebral-deposition-in-the-app23-transgenic-mouse-model-of-alzheimer-s-disease
#5
Sofía Fernández-de Retana, Alex Montañola, Paula Marazuela, Maialen De La Cuesta, Aina Batlle, Marc Fatar, Saskia Grudzenski, Joan Montaner, Mar Hernández-Guillamon
Beyond the crucial role of apolipoprotein A-I (ApoA-I) on peripheral cholesterol metabolism, this apolipoprotein has also been implicated in beta amyloid (Aβ)-related neuropathologies. ApoA-I-Milano (M) is a mutated variant, which showed increased vasoprotective properties compared to ApoA-I-wild type in models of atherosclerosis and cardiovascular damage. We speculated that ApoA-I-M may also protect Aβ-affected vasculature and reverse some of the pathological features associated with Alzheimer's disease (AD)...
September 5, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28934192/metabolomics-and-cognition-in-african-american-adults-in-midlife-the-atherosclerosis-risk-in-communities-study
#6
J Bressler, B Yu, T H Mosley, D S Knopman, R F Gottesman, A Alonso, A R Sharrett, L M Wruck, E Boerwinkle
Clinical studies have shown alterations in metabolic profiles when patients with mild cognitive impairment and Alzheimer's disease dementia were compared to cognitively normal subjects. Associations between 204 serum metabolites measured at baseline (1987-1989) and cognitive change were investigated in 1035 middle-aged community-dwelling African American participants in the biracial Atherosclerosis Risk in Communities (ARIC) Study. Cognition was evaluated using the Delayed Word Recall Test (DWRT; verbal memory), the Digit Symbol Substitution Test (DSST; processing speed) and the Word Fluency Test (WFT; verbal fluency) at visits 2 (1990-1992) and 4 (1996-1998)...
July 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28916531/diabetes-prediabetes-and-brain-volumes-and-subclinical-cerebrovascular-disease-on-mri-the-atherosclerosis-risk-in-communities-neurocognitive-study-aric-ncs
#7
Andrea L C Schneider, Elizabeth Selvin, A Richey Sharrett, Michael Griswold, Josef Coresh, Clifford R Jack, David Knopman, Thomas Mosley, Rebecca F Gottesman
OBJECTIVE: To examine the associations of prediabetes, diabetes, and diabetes severity (as assessed by HbA1c and diabetes duration) with brain volumes and vascular pathology on brain MRI and to assess whether the associations of diabetes with brain volumes are mediated by brain vascular pathology. RESEARCH DESIGN AND METHODS: Cross-sectional study of 1,713 participants in the Atherosclerosis Risk in Communities Neurocognitive Study (mean age 75 years, 60% female, 27% black, 30% prediabetes, and 35% diabetes) who underwent 3T brain MRI scans in 2011-2013...
September 15, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28901253/bacterial-toxins-a-hope-towards-angiogenic-ailments
#8
Rekha Khandia, Ashok Kumar Munjal, Kuldeep Dhama, Yashpal Singh Malik
Angiogenesis is a vital physiological process essential for growth and maintenance of the body. It plays an important role during embryonic development and generally absent in adults with some exceptions like during wound repair and menstrual cycle in women. Excess as well as deficiency in angiogenesis, result in pathological conditions. It is a tightly regulated process; rely on cascade of several molecular signalling pathways involving many effectors like VEGF, FGF, PDGF, IGF etc. Excessive angiogenesis is associated with disorders like tumor, atherosclerosis, rheumatoid arthritis, diabetic retinopathy, endometriosis, psoriasis, adiposity...
September 11, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28888831/steryl-ester-synthesis-storage-and-hydrolysis-a-contribution-to-sterol-homeostasis
#9
REVIEW
Martina Korber, Isabella Klein, Günther Daum
Sterols are essential lipids of all eukaryotic cells, appearing either as free sterols or steryl esters. Besides other regulatory mechanisms, esterification of sterols and hydrolysis of steryl esters serve to buffer both an excess and a lack of free sterols. In this review, the esterification process, the storage of steryl esters and their mobilization will be described. Several model organisms are discussed but the focus was set on mammals and the yeast Saccharomyces cerevisiae. The contribution of imbalanced cholesterol homeostasis to several human diseases, namely Wolman disease, cholesteryl ester storage disease, atherosclerosis and Alzheimer's disease, Niemann-Pick type C and Tangier disease is described...
December 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28810593/carotid-atherosclerosis-promotes-the-progression-of-alzheimer-s-disease-a-three-year-prospective-study
#10
Jing Xiang
Although cerebrovascular diseases have been considered as risk factors for cognitive decline and dementia, the associations between atherosclerosis and Alzheimer's disease (AD) have not been fully examined and remain controversial. The aim of this three-year prospective study was to investigate whether arotid artery atherosclerosis accelerates cognitive impairment in AD patients. The association of carotid intimal medial thickness (IMT) with prospective trajectories of cognitive function was assessed among 521 patients with light to moderate AD, and 437 AD patients were followed up annually for 3 years...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28800073/electronegative-low-density-lipoprotein-l5-impairs-viability-and-ngf-induced-neuronal-differentiation-of-pc12-cells-via-lox-1
#11
Jiz-Yuh Wang, Chiou-Lian Lai, Ching-Tien Lee, Chen-Yen Lin
There have been striking associations of cardiovascular diseases (e.g., atherosclerosis) and hypercholesterolemia with increased risk of neurodegeneration including Alzheimer's disease (AD). Low-density lipoprotein (LDL), a cardiovascular risk factor, plays a crucial role in AD pathogenesis; further, L5, a human plasma LDL fraction with high electronegativity, may be a factor contributing to AD-type dementia. Although L5 contributing to atherosclerosis progression has been studied, its role in inducing neurodegeneration remains unclear...
August 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28777829/identification-of-an-early-transcriptomic-signature-of-insulin-resistance-and-related-diseases-in-lymphomonocytes-of-healthy-subjects
#12
Alice Matone, Eleonora Derlindati, Luca Marchetti, Valentina Spigoni, Alessandra Dei Cas, Barbara Montanini, Diego Ardigò, Ivana Zavaroni, Corrado Priami, Riccardo C Bonadonna
Insulin resistance is considered to be a pathogenetic mechanism in several and diverse diseases (e.g. type 2 diabetes, atherosclerosis) often antedating them in apparently healthy subjects. The aim of this study is to investigate with a microarray based approach whether IR per se is characterized by a specific pattern of gene expression. For this purpose we analyzed the transcriptomic profile of peripheral blood mononuclear cells in two groups (10 subjects each) of healthy individuals, with extreme insulin resistance or sensitivity, matched for BMI, age and gender, selected within the MultiKnowledge Study cohort (n = 148)...
2017: PloS One
https://www.readbyqxmd.com/read/28740175/genetic-and-functional-characterization-of-disease-associations-explains-comorbidity
#13
Carlota Rubio-Perez, Emre Guney, Daniel Aguilar, Janet Piñero, Javier Garcia-Garcia, Barbara Iadarola, Ferran Sanz, Narcís Fernandez-Fuentes, Laura I Furlong, Baldo Oliva
Understanding relationships between diseases, such as comorbidities, has important socio-economic implications, ranging from clinical study design to health care planning. Most studies characterize disease comorbidity using shared genetic origins, ignoring pathway-based commonalities between diseases. In this study, we define the disease pathways using an interactome-based extension of known disease-genes and introduce several measures of functional overlap. The analysis reveals 206 significant links among 94 diseases, giving rise to a highly clustered disease association network...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738188/sleep-characteristics-and-risk-of-dementia-and-alzheimer-s-disease-the-atherosclerosis-risk-in-communities-study
#14
Pamela L Lutsey, Jeffrey R Misialek, Thomas H Mosley, Rebecca F Gottesman, Naresh M Punjabi, Eyal Shahar, Richard MacLehose, Rachel P Ogilvie, David Knopman, Alvaro Alonso
INTRODUCTION: This study tested the hypotheses that late-midlife obstructive sleep apnea (OSA) and short and long sleep duration are associated with dementia over 15 years of follow-up. METHODS: A total of 1667 Atherosclerosis Risk in Communities Study participants underwent in-home polysomnography (1996-1998) and were followed for dementia. Dementia was defined by (1) hospitalization diagnosis codes (1996-2012) and (2) a comprehensive neurocognitive examination (2011-2013) with adjudication...
July 21, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28731362/greater-cognitive-deficits-with-sleep-disordered-breathing-among-individuals-with-genetic-susceptibility-to-alzheimer-s-disease-the-multi-ethnic-study-of-atherosclerosis
#15
Dayna A Johnson, Jacqueline Lane, Rui Wang, Michelle Reid, Ina Djonlagic, Annette L Fitzpatrick, Stephen R Rapp, Luenda E Charles, Ruth O'Hara, Richa Saxena, Susan Redline
RATIONALE: There are conflicting findings regarding the link between sleep apnea and cognitive dysfunction. OBJECTIVE: Investigate associations between indicators of sleep-disordered breathing (SDB) and cognitive function in the Multi-Ethnic Study of Atherosclerosis and assess effect modification by the apolipoprotein ε-4 (APOE-ε4) allele. METHODS: A diverse population (N=1,752) underwent Type 2 in-home polysomnography, which included measurement of % sleep time <90% oxyhemoglobin saturation (%Sat<90%) and apnea-hypopnea index (AHI)...
July 21, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28704393/whole-exome-sequence-based-association-analyses-of-plasma-amyloid-%C3%AE-in-african-and-european-americans-the-atherosclerosis-risk-in-communities-neurocognitive-study
#16
Jeannette Simino, Zhiying Wang, Jan Bressler, Vincent Chouraki, Qiong Yang, Steven G Younkin, Sudha Seshadri, Myriam Fornage, Eric Boerwinkle, Thomas H Mosley
OBJECTIVE: We performed single-variant and gene-based association analyses of plasma amyloid-β (aβ) concentrations using whole exome sequence from 1,414 African and European Americans. Our goal was to identify genes that influence plasma aβ42 concentrations and aβ42:aβ40 ratios in late middle age (mean = 59 years), old age (mean = 77 years), or change over time (mean = 18 years). METHODS: Plasma aβ measures were linearly regressed onto age, gender, APOE ε4 carrier status, and time elapsed between visits (fold-changes only) separately by race...
2017: PloS One
https://www.readbyqxmd.com/read/28699112/brain-under-stress-and-alzheimer-s-disease
#17
REVIEW
Boris Mravec, Lubica Horvathova, Alexandra Padova
Modern society is characterized by the ubiquity of stressors that affect every individual to different extents. Furthermore, experimental, clinical, and epidemiological data have shown that chronic activation of the stress response may participate in the development of various somatic as well as neuropsychiatric diseases. Surprisingly, the role that stress plays in the etiopathogenesis of Alzheimer's disease (AD) has not yet been studied in detail and is therefore not well understood. However, accumulated data have shown that neuroendocrine and behavioral changes accompanying the stress response affect neuronal homeostasis and compromise several key neuronal processes...
July 11, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28693132/expression-of-4-hydroxynonenal-in-esophageal-squamous-cell-carcinoma
#18
Ying Zhang, Hu Wang, Kezhou Wu, Zhaoyong Liu
Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer in Asia, particular in China. However, the pathogenesis of ESCC has not previously been well demonstrated. A major product of lipid peroxidation, 4-hydroxynonenal (4-HNE), is considered to be an oxidative stress inducer, as it is involved in the pathogenesis of a number of degenerative diseases, including Alzheimer's disease, atherosclerosis, cataracts and cancer. In order to investigate the association between oxidative stress and the pathogenic process of ESCC, the present study determined the expression levels of 4-HNE in 23 non-malignant esophageal epithelial tissues, 11 esophageal carcinoma in situ tissues and 57 ESCC tissues from patients in the Chaoshan area, a high-risk region for esophageal cancer in China...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28687876/chromosome-21-encoded-micrornas-mrnas-impact-on-down-s-syndrome-and-trisomy-21-linked-disease
#19
P N Alexandrov, M E Percy, Walter J Lukiw
Down's syndrome (DS; also known as trisomy 21; T21) is caused by a triplication of all or part of human chromosome 21 (chr21). DS is the most common genetic cause of intellectual disability attributable to a naturally-occurring imbalance in gene dosage. DS incurs huge medical, healthcare, and socioeconomic costs, and there are as yet no effective treatments for this incapacitating human neurogenetic disorder. There is a remarkably wide variability in the 'phenotypic spectrum' associated with DS; the progression of symptoms and the age of DS onset fluctuate, and there is further variability in the biophysical nature of the chr21 duplication...
July 7, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28630235/ultrasound-markers-of-carotid-atherosclerosis-and-cognition-the-northern-manhattan-study
#20
Hannah Gardener, Michelle R Caunca, Chuanhui Dong, Ying Kuen Cheung, Mitchell S V Elkind, Ralph L Sacco, Tatjana Rundek, Clinton B Wright
BACKGROUND AND PURPOSE: Ultrasound markers of carotid atherosclerosis may be related to cognitive status. We hypothesized that individuals with greater carotid intima-media thickness (cIMT) and carotid plaque burden would exhibit worse cognition. METHODS: One thousand one hundred sixty-six stroke-free participants from the NOMAS (Northern Manhattan Study) underwent carotid ultrasound and neuropsychological examination. Among them, 826 underwent a second neuropsychological examination an average of 5 years later...
July 2017: Stroke; a Journal of Cerebral Circulation
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