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Tobias Skillbäck, Ronald Lautner, Niklas Mattsson, Jonathan M Schott, Katarina Nägga, Lena Kilander, Anders Wimo, Bengt Winblad, Maria Eriksdotter, Kaj Blennow, Henrik Zetterberg
INTRODUCTION: The ε4 allele of the apolipoprotein E (APOE) gene is a prominent risk factor for Alzheimer's disease (AD), but its implication in other dementias is less well studied. METHODS: We used a data set on 2858 subjects (1098 AD, 260 vascular dementia [VaD], 145 mixed AD and VaD, 90 other dementia diagnoses, and 1265 controls) to examine the association of APOE polymorphisms with clinical dementia diagnoses, biomarker profiles, and longevity. RESULTS: The ε4 allele was associated with reduced longevity as ε4 versus ε3 homozygotes lived on average 2...
March 13, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Corinna Schmitz, Heidi Noels, Omar El Bounkari, Eva Straussfeld, Remco T A Megens, Marieke Sternkopf, Setareh Alampour-Rajabi, Christine Krammer, Pathricia V Tilstam, Norbert Gerdes, Christina Bürger, Aphrodite Kapurniotu, Richard Bucala, Joachim Jankowski, Christian Weber, Jürgen Bernhagen
The inflammatory cytokine macrophage migration-inhibitory factor (MIF) promotes atherosclerosis via lesional monocyte and T-cell recruitment. B cells have emerged as important components in atherogenesis, but the interaction between MIF and B cells in atherogenesis is unknown. Here, we investigated the atherosclerotic phenotype of Mif-gene deletion in Apoe-/- mice. Apoe-/- Mif-/- mice on a Western-diet exhibited strongly reduced atherosclerotic lesions in brachiocephalic artery (BC) and abdominal aorta compared with controls...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Valentin Blanchard, Stephane Ramin-Mangata, Stephanie Billon-Crossouard, Audrey Aguesse, Manon Durand, Kevin Chemello, Brice Nativel, Laurent Flet, Maud Chetiveaux, David Jacobi, Jean-Marie Bard, Khadija Ouguerram, Gilles Lambert, Michel Krempf, Mikael Croyal
Human apolipoprotein E (apoE) exhibits three major isoforms (apoE2, apoE3, and apoE4) corresponding to polymorphism in the APOE gene. Total plasma apoE concentrations are closely related to these isoforms but the underlying mechanisms are unknown. We aimed to describe the kinetics of apoE individual isoforms to explore the mechanisms for variable total apoE plasma concentrations. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to discriminate between isoforms by identifying specific peptide sequences in subjects (3 E2/E3, 3 E3/E3 and 3 E3/E4 phenotypes) who received a primed constant infusion of2 H3 -leucine for 14 hours...
March 14, 2018: Journal of Lipid Research
Liv Tybjærg Nordestgaard, Anne Tybjærg-Hansen, Katrine Laura Rasmussen, Børge G Nordestgaard, Ruth Frikke-Schmidt
BACKGROUND: Clusterin, also known as apolipoprotein J (apoJ), is one of the most abundantly expressed apolipoproteins in the brain after apolipoprotein E (apoE). Like the ε4 allele of the apolipoprotein E gene (APOE), the clusterin gene (CLU) is a risk locus for Alzheimer's disease, and may play additional roles in atherosclerosis pathogenesis. We tested whether genetic variation in CLU was associated with either Alzheimer's disease or atherosclerosis-related diseases. METHODS: We studied individual data on 103,987 participants from the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS)...
March 14, 2018: BMC Medicine
Po-Jung Pao, Eszter Emri, Safiya Bishar Abdirahman, Talha Soorma, Hui-Hui Zeng, Stefanie M Hauck, Richard B Thompson, Imre Lengyel
Population-based and interventional studies have shown that elevated zinc levels can reduce the progression to advanced age-related macular degeneration. The objective of this study was to assess whether elevated extracellular zinc has a direct effect on retinal pigment epithelial cells (RPE), by examining the phenotype and molecular characteristics of increased extracellular zinc on human primary RPE cells. Monolayers of human foetal primary RPE cells were grown on culture inserts and maintained in medium supplemented with increasing total concentrations of zinc (0, 75, 100, 125 and 150 μM) for up to 4 weeks...
March 1, 2018: Journal of Trace Elements in Medicine and Biology
Xue-Na Zheng, Jun Yang, Tao Xie, Bin Guo, Zhi-Qiang Xie, Li-Na Xie, Xue-Fen Wu, Gang-Zhu Hu, Mai-Lan Liu, Zeng-Hui Yue
OBJECTIVE: To observe the effect of herbal cake-separated moxibustion on blood lipid-apoprotein levels and the expression of Toll-like receptor 2 (TLR 2), TLR 4 and nuclear factor kappa B(NF-κB) mRNAs in atherosclerotic (AS) vulnerable plaques of hyperglycemia rabbits, so as to explore its mechanism underlying improvement of atherosclerosis. METHODS: Sixty New Zealand rabbits were randomly divided into 5 groups: control, model, direct moxibustion, herbal-cake-separated moxibustion and medication groups( n =12 rabbits in each group)...
February 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
Ling Li, Fan Zeng, Yu-Hui Liu, Hui-Yun Li, Shu-Yang Dong, Ze-Yan Peng, Yan-Jiang Wang, Hua-Dong Zhou
Polymorphisms of the cholesterol-24S-hydroxylase (CYP46A1) and apolipoprotein E (APOE) genes are risk factors for Alzheimer's disease (AD). Plasma level of 24S-hydroxcholesterol (24-OHC), the metabolite of cholesterol, is thought to correlate with AD. The present study investigated the correlation between these genetic factors and blood 24-OHC and amyloid-beta (Aβ) levels in AD patients. Association analysis, logistic regression, and linear regression were used to analyze the correlation of CYP46A1 and APOE genotypes with blood 24-OHC and Aβ levels and AD risk...
March 7, 2018: Molecular Neurobiology
Ida K Karlsson, Alexander Ploner, Yunzhang Wang, Margaret Gatz, Nancy L Pedersen, Sara Hägg
Background: This study aims to investigate if DNA methylation of the apolipoprotein E (APOE) locus affects the risks of dementia, Alzheimeŕs disease (AD) or cardiovascular disease (CVD). Methods: DNA methylation across the APOE gene has previously been categorized into three distinct regions: a hypermethylated region in the promoter, a hypomethylated region in the first two introns and exons and a hypermethylated region in the 3'exon that also harbours the APOE ε2 and ε4 alleles...
March 2, 2018: International Journal of Epidemiology
Zhengsheng Zhang, Xiang-Yan Chen, Larry Baum, Ho Keung Ng, Vincent Mok, Ka Sing Wong
OBJECTIVES: Stenosis of the intracranial large arteries, especially the middle cerebral artery (MCA), is common in the Chinese population. We conducted a case-control study to investigate clinical and apolipoprotein E (ApoE) gene polymorphism of MCA atherosclerosis in the Chinese population. MATERIALS AND METHODS: Polymerase chain reaction-based protocols were used to identify the genotypes of polymorphisms in ApoE genes. Clinical parameters and the genotypes of polymorphisms in the ApoE genes were compared in patients with and without MCA stenosis...
March 2018: Neurologist
Eoin P Brennan, Muthukumar Mohan, Aaron McClelland, Christos Tikellis, Mark Ziemann, Antony Kaspi, Stephen P Gray, Raelene Pickering, Sih Min Tan, Syed Tasadaque Ali-Shah, Patrick J Guiry, Assam El-Osta, Karin Jandeleit-Dahm, Mark E Cooper, Catherine Godson, Phillip Kantharidis
Background The failure of spontaneous resolution underlies chronic inflammatory conditions, including microvascular complications of diabetes such as diabetic kidney disease. The identification of endogenously generated molecules that promote the physiologic resolution of inflammation suggests that these bioactions may have therapeutic potential in the context of chronic inflammation. Lipoxins (LXs) are lipid mediators that promote the resolution of inflammation. Methods We investigated the potential of LXA4 and a synthetic LX analog (Benzo-LXA4 ) as therapeutics in a murine model of diabetic kidney disease, ApoE-/- mice treated with streptozotocin...
February 28, 2018: Journal of the American Society of Nephrology: JASN
Elizabeth E Blue, Joshua C Bis, Michael O Dorschner, Debby W Tsuang, Sandra M Barral, Gary Beecham, Jennifer E Below, William S Bush, Mariusz Butkiewicz, Carlos Cruchaga, Anita DeStefano, Lindsay A Farrer, Alison Goate, Jonathan Haines, Jim Jaworski, Gyungah Jun, Brian Kunkle, Amanda Kuzma, Jenny J Lee, Kathryn L Lunetta, Yiyi Ma, Eden Martin, Adam Naj, Alejandro Q Nato, Patrick Navas, Hiep Nguyen, Christiane Reitz, Dolly Reyes, William Salerno, Gerard D Schellenberg, Sudha Seshadri, Harkirat Sohi, Timothy A Thornton, Otto Valadares, Cornelia van Duijn, Badri N Vardarajan, Li-San Wang, Eric Boerwinkle, Josée Dupuis, Margaret A Pericak-Vance, Richard Mayeux, Ellen M Wijsman
BACKGROUND/AIMS: The Alzheimer's Disease Sequencing Project (ADSP) aims to identify novel genes influencing Alzheimer's disease (AD). Variants within genes known to cause dementias other than AD have previously been associated with AD risk. We describe evidence of co-segregation and associations between variants in dementia genes and clinically diagnosed AD within the ADSP. METHODS: We summarize the properties of known pathogenic variants within dementia genes, describe the co-segregation of variants annotated as "pathogenic" in ClinVar and new candidates observed in ADSP families, and test for associations between rare variants in dementia genes in the ADSP case-control study...
February 27, 2018: Dementia and Geriatric Cognitive Disorders
Guo-Qiang Yuan, Song Gao, Yong-Jian Geng, Yao-Ping Tang, Min-Juan Zheng, Harnath S Shelat, Scott Collins, Han-Jing Wu, Yi-Ling Wu
Background: Our previous studies have shown that Tongxinluo (TXL), a compound Chinese medicine, can decrease myocardial ischemia-reperfusion injury, protect capillary endothelium function, and lessen cardiac ventricle reconstitution in animal models. The aim of this study was to illuminate whether TXL can improve hypercholesterolemia-impaired heart function by protecting artery endothelial function and increasing microvascular density (MVD) in heart. Furthermore, we will explore the underlying molecular mechanism of TXL cardiovascular protection...
March 5, 2018: Chinese Medical Journal
Jason D Ulrich, Tyler K Ulland, Thomas E Mahan, Sofie Nyström, K Peter Nilsson, Wilbur M Song, Yingyue Zhou, Mariska Reinartz, Seulah Choi, Hong Jiang, Floy R Stewart, Elise Anderson, Yaming Wang, Marco Colonna, David M Holtzman
One of the hallmarks of Alzheimer's disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-β (Aβ) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aβ in the brain. In addition to influencing Aβ metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1ΔE9 and APPPS1-21 transgenic mice...
February 26, 2018: Journal of Experimental Medicine
Zhixiong Zhong, Heming Wu, Min Ye, Yuxian Yang, Weixiong Luo, Yanli Wu, Hesen Wu, Miaocai Zhong, Pingsen Zhao
BACKGROUND Apolipoprotein E (ApoE) is a multifunctional protein that plays an important role in lipoprotein metabolism. However, the relationship between APOE gene polymorphisms and cerebral infarction in the Chinese population remains unclear. Therefore, we studied the role of APOE gene polymorphisms in patients with cerebral infarction in a Chinese population. MATERIAL AND METHODS This study involved 906 patients with cerebral infarction and 1,141 individuals without cerebral infarction who served as controls...
February 26, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Wenjing Liang, Qian Wang, Hui Ma, Wenjiang Yan, Jingjing Yang
BACKGROUND/AIMS: Fibroblast growth factor 2 (FGF2) plays a predominant role during angiogenesis in the adventitia and in atherosclerotic plaque. A dilemma exists, however, as to whether angiogenic stimulation by FGF2 for the prevention and treatment of atherogenesis is feasible. The aim of this study is to investigate the effect of the 18-kDa FGF-2 isoform on atherosclerosis progression in high-fat diet-fed apolipoprotein E knockout (ApoE-/-) mice. METHODS: We established a model of atherosclerosis using ApoE and 18-kDa FGF-2 gene double knockout mice...
February 16, 2018: Cellular Physiology and Biochemistry
Isabel Quesada, Jimena Cejas, Rodrigo García, Beatriz Cannizzo, Analía Redondo, Claudia Castro
AIM: Perivascular adipose tissue (PVAT) is in intimate contact with the vessel wall and extravascular PVAT-derived inflammatory mediators may adversely influence atherosclerotic plaque formation and stability through outside-to-inside signalling. We sought to investigate the role of PVAT on the atheroma development in an experimental animal model of Metabolic Syndrome (MS) associated with oxidative stress and low-grade inflammatory state. We also studied the effect of Pioglitazone an insulin sensitizer, on the aortic wall and its surrounding PVAT, considering a bi-directional communication between both layers...
February 21, 2018: Cardiovascular Therapeutics
Victoria C Merritt, Alexandra L Clark, Scott F Sorg, Nicole D Evangelista, Madeleine Werhane, Mark W Bondi, Dawn M Schiehser, Lisa Delano-Wood
Since few studies have examined the relationship between the APOE gene and clinical outcomes following military-related traumatic brain injury (TBI), we aimed to determine whether the ε4 allele of the APOE gene influences neuropsychiatric symptoms in Veterans with a history of mild to moderate TBI. Participants included 133 Veterans (TBI=79, military controls [MC]=54) who underwent APOE genotyping and were divided into ε4+ (TBI=18, MC=15) and ε4- (TBI=61, MC=39) groups. All participants underwent evaluation of psychological distress using the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and PTSD Checklist-Military Version (PCL-M)...
February 20, 2018: Journal of Neurotrauma
Difei Wang, Huiying Cong, Xiaoli Wang, Yanli Cao, Shoichiro Ikuyama, Bin Fan, Jianqiu Gu
Pycnogenol (PYC), a combination of active flavonoids derived from French maritime pine bark, is a natural antioxidant that has various pharmacological activities. Here, we investigated the beneficial effect of PYC on diet-induced hepatic steatosis. Apolipoprotein E (ApoE)-deficient male mice were administered PYC at oral doses of 30 or 100 mg•kg-1 •day-1 for two weeks in advance and were then fed a high cholesterol and fat diet (HCD) for eight weeks. Biochemical, immunohistochemical, and gene expression analyses were conducted to explore the effect of PYC on lipid metabolism in ApoE-deficient mice on a HCD...
February 20, 2018: American Journal of Physiology. Endocrinology and Metabolism
Yongliang Zhao, Yiqing Yang, Roumei Xing, Xueqin Cui, Yufang Xiao, Ling Xie, Panpan You, Tongtong Wang, Li Zeng, Wenhui Peng, Dali Li, Huaqing Chen, Mingyao Liu
BACKGROUND AND AIMS: Low-density lipoprotein receptor (Ldlr) and apolipoprotein E (Apoe) knockout (KO) mice have been widely used as animal models of atherosclerosis. However, data suggested that it is difficult to develop typical atherosclerosis in rats. To this end, Ldlr and Apoe KO rats were generated and the potential to develop novel atherosclerosis models was evaluated. METHODS: We established Apoe/Ldlr single and double KO (DKO) rats via the CRISPR/Cas9 system in the same background...
February 12, 2018: Atherosclerosis
Yanal A Shafagoj, Randa G Naffa, Mohammed S El-Khateeb, Yazeed L Abdulla, Aseem A Al-Qaddoumi, Faisal A Khatib, Yousef F Al-Motassem, Eman M Al-Khateeb
OBJECTIVE: To investigate the frequencies of the apolipoprotein E (APOE) alleles and genotypes and study their relationship with the lipid profile in Jordanian patients with late-onset Alzheimer`s disease (AD). METHODS: This case-control study was carried out on 71 Jordanian individuals: 38 patients with late-onset AD (age >/=65 years) and 33 age-matched healthy controls. All participants were recruited from senior homes and Jordan University Hospital, Amman, Jordan between January 2010 and December 2013...
January 2018: Neurosciences: the Official Journal of the Pan Arab Union of Neurological Sciences
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