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Apolipoprotein E

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https://www.readbyqxmd.com/read/28342882/functional-neuroimaging-findings-in-healthy-middle-aged-adults-at-risk-of-alzheimer-s-disease
#1
REVIEW
Mirette Habib, Elijah Mak, Silvy Gabel, Li Su, Guy Williams, Adam Waldman, Katie Wells, Karen Ritchie, Craig Ritchie, John T O'Brien
It is well established that the neurodegenerative process of Alzheimer's disease (AD) begins many years before symptom onset. This preclinical phase provides a crucial time-window for therapeutic intervention, though this requires biomarkers that could evaluate the efficacy of future disease-modification treatments in asymptomatic individuals. The last decade has witnessed a proliferation of studies characterizing the temporal sequence of the earliest functional and structural brain imaging changes in AD. These efforts have focused on studying individuals who are highly vulnerable to develop AD, such as those with familial genetic mutations, susceptibility genes (i...
March 22, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28336201/a-facile-method-for-isolation-of-recombinant-human-apolipoprotein-a-i-from-e-coli
#2
Nikita Ikon, Jennifer Shearer, Jianfang Liu, Jesse J Tran, ShiBo Feng, Ayako Kamei, Jennifer A Beckstead, Robert S Kiss, Paul M Weers, Gang Ren, Robert O Ryan
Apolipoprotein (apo) A-I is the major protein component of high-density lipoprotein (HDL) and plays key roles in the Reverse Cholesterol Transport pathway. In the past decade, reconstituted HDL (rHDL) has been employed as a therapeutic agent for treatment of atherosclerosis. The ability of rHDL to promote cholesterol efflux from peripheral cells has been documented to reduce the size of atherosclerotic plaque lesions. However, development of apoA-I rHDL-based therapeutics for human use requires a cost effective process to generate an apoA-I product that meets "Good Manufacturing Practice" standards...
March 20, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28335839/apolipoprotein-l1-variants%C3%A2-and-blood-pressure-traits-in%C3%A2-african-americans
#3
Girish N Nadkarni, Geneviève Galarneau, Stephen B Ellis, Rajiv Nadukuru, Jinglan Zhang, Stuart A Scott, Claudia Schurmann, Rongling Li, Laura J Rasmussen-Torvik, Abel N Kho, M Geoffrey Hayes, Jennifer A Pacheco, Teri A Manolio, Rex L Chisholm, Dan M Roden, Joshua C Denny, Eimear E Kenny, Erwin P Bottinger
BACKGROUND: African Americans (AA) are disproportionately affected by hypertension-related health disparities. Apolipoprotein L1 (APOL1) risk variants are associated with kidney disease in hypertensive AAs. OBJECTIVES: This study assessed the APOL1 risk alleles' association with blood pressure traits in AAs. METHODS: The discovery cohort included 5,204 AA participants from Mount Sinai's BioMe biobank. Replication cohorts included additional BioMe (n = 1,623), Vanderbilt BioVU (n = 1,809), and Northwestern NUgene (n = 567) AA biobank participants...
March 28, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28335828/dha-brain-uptake-and-apoe4-status-a-pet-study-with-1-11-c-dha
#4
Hussein N Yassine, Etienne Croteau, Varun Rawat, Joseph R Hibbeln, Stanley I Rapoport, Stephen C Cunnane, John C Umhau
BACKGROUND: The apolipoprotein E ɛ4 (APOE4) allele is the strongest genetic risk factor identified for developing Alzheimer's disease (AD). Among brain lipids, alteration in the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) homeostasis is implicated in AD pathogenesis. APOE4 may influence both brain DHA metabolism and cognitive outcomes. METHODS: Using positron emission tomography, regional incorporation coefficients (k*), rates of DHA incorporation from plasma into the brain using [1-(11)C]-DHA (J in), and regional cerebral blood flow using [(15)O]-water were measured in 22 middle-aged healthy adults (mean age 35 years, range 19-65 years)...
March 23, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28335021/mri-visible-perivascular-space-location-is-associated-with-alzheimer-s-disease-independently-of-amyloid-burden
#5
Gargi Banerjee, Hee Jin Kim, Zoe Fox, H Rolf Jäger, Duncan Wilson, Andreas Charidimou, Han Kyu Na, Duk L Na, Sang Won Seo, David J Werring
Perivascular spaces that are visible on magnetic resonance imaging (MRI) are a neuroimaging marker of cerebral small vessel disease. Their location may relate to the type of underlying small vessel pathology: those in the white matter centrum semi-ovale have been associated with cerebral amyloid angiopathy, while those in the basal ganglia have been associated with deep perforating artery arteriolosclerosis. As cerebral amyloid angiopathy is an almost invariable pathological finding in Alzheimer's disease, we hypothesized that MRI-visible perivascular spaces in the centrum semi-ovale would be associated with a clinical diagnosis of Alzheimer's disease, whereas those in the basal ganglia would be associated with subcortical vascular cognitive impairment...
February 17, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28333036/apoe-%C3%AE%C2%B54-specific-imbalance-of-arachidonic-acid-and-docosahexaenoic-acid-in-serum-phospholipids-identifies-individuals-with-preclinical-mild-cognitive-impairment-alzheimer-s-disease
#6
Laila Abdullah, James E Evans, Tanja Emmerich, Gogce Crynen, Ben Shackleton, Andrew P Keegan, Cheryl Luis, Leon Tai, Mary J LaDu, Michael Mullan, Fiona Crawford, Corbin Bachmeier
This study was designed to explore the influence of apolipoprotein E (APOE) on blood phospholipids (PL) in predicting preclinical Alzheimer's disease (AD). Lipidomic analyses were also performed on blood from an AD mouse model expressing human APOE isoforms (EFAD) and five AD mutations and from 195 cognitively normal participants, 23 of who converted to mild cognitive impairment (MCI)/AD within 3 years. APOE ε4-carriers converting to MCI/AD had high arachidonic acid (AA)/docosahexaenoic acid (DHA) ratios in PL compared to cognitively normal ε4 and non-ε4 carriers...
March 23, 2017: Aging
https://www.readbyqxmd.com/read/28330873/amp-activated-protein-kinase-%C3%AE-1-promotes-atherogenesis-by-increasing-monocyte-to-macrophage-differentiation
#7
Miao Zhang, Huaiping Zhu, Ye Ding, Zhaoyu Liu, Zhejun Cai, Ming-Hui Zou
Monocyte-to-macrophage differentiation, which can be initiated by physiological or atherogenic factors, is a pivotal process in atherogenesis, a disorder in which monocytes adhere to endothelial cells and subsequently migrate into the sub-endothelial spaces, where they differentiate into macrophages and macrophage-derived foam cells and cause atherosclerotic lesions. However, the monocyte-differentiation signaling pathways that are activated by atherogenic factors are poorly defined. Here we report that the AMP- activated protein kinase (AMPK) α1 in monocytes promotes atherosclerosis by increasing monocyte differentiation and survival...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28330813/atp-binding-cassette-transporter-a1-deficiency-in-human-induced-pluripotent-stem-cell-derived-hepatocytes-abrogates-hdl-biogenesis-and-enhances-triglyceride-secretion
#8
Xin Bi, Evanthia E Pashos, Marina Cuchel, Nicholas N Lyssenko, Mayda Hernandez, Antonino Picataggi, James McParland, Wenli Yang, Ying Liu, Ruilan Yan, Christopher Yu, Stephanie L DerOhannessian, Michael C Phillips, Edward E Morrisey, Stephen A Duncan, Daniel J Rader
Despite the recognized role of the ATP-binding Cassette Transporter A1 (ABCA1) in high-density lipoprotein (HDL) metabolism, our understanding of ABCA1 deficiency in human hepatocytes is limited. To define the functional effects of human hepatocyte ABCA1 deficiency, we generated induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) from Tangier disease (TD) and matched control subjects. Control HLCs exhibited robust cholesterol efflux to apolipoprotein A-I (apoA-I) and formed nascent HDL particles...
March 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28330509/chemically-treated-plasma-a%C3%AE-is-a-potential-blood-based-biomarker-for-screening-cerebral-amyloid-deposition
#9
Jong-Chan Park, Sun-Ho Han, Hyun Jin Cho, Min Soo Byun, Dahyun Yi, Young Min Choe, Seokjo Kang, Eun Sun Jung, Su Jin Won, Eun Hye Kim, Yu Kyeong Kim, Dong Young Lee, Inhee Mook-Jung
BACKGROUND: Plasma β-amyloid (Aβ) is a potential candidate for an Alzheimer's disease (AD) biomarker because blood is an easily accessible bio-fluid, which can be collected routinely, and Aβ is one of the major hallmarks of AD pathogenesis in the brain. However, the association between plasma Aβ levels and AD diagnosis is still unclear due to the instability and inaccurate measurements of plasma Aβ levels in the blood of patients with AD. If a consistent value of plasma Aβ from the blood can be obtained, this might help determine whether plasma Aβ is a potential biomarker for AD diagnosis...
March 22, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28326331/effects-of-apolipoprotein-e-isoforms-in-diabetic-nephropathy-of-chinese-type-2-diabetic-patients
#10
YongWei Jiang, Liang Ma, ChengWu Han, Qian Liu, Xiao Cong, YaPing Xu, TingTing Zhao, Ping Li, YongTong Cao
Diabetic nephropathy (DN) is one of the major chronic complications of diabetes. Genetic polymorphism of Apolipoprotein E (ApoE) has been proposed to participating in DN. The purpose of the study was to evaluate the relationship between ApoE genetic polymorphism and the presence of DN in Chinese type 2 diabetic patients. We studied 845 diabetic patients who were divided into DN group (n = 429) and control group (n = 416). ApoE genotype was determined by ApoE genotyping chip and the plasmatic biochemical characterization was performed on all subjects...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28326151/chronic-porphyromonas-gingivalis-infection-accelerates-the-occurrence-of-age-related-granules-in-apoe-mice-brains
#11
Sim K Singhrao, Sasanka Chukkapalli, Sophie Poole, Irina Velsko, St John Crean, Lakshmyya Kesavalu
This study explored the origin of age-related granules in the apolipoprotein E gene knockout (ApoE(-/-)) B6 background mice brains following chronic gingival infection with Porphyromonas gingivalis for 24 weeks. Intracerebral localization of P. gingivalis was detected by fluorescence in situ hybridization (FISH) and its protease by immunohistochemistry. The age-related granules were observed by periodic acid-Schiff (PAS), silver impregnation, and immunostaining. FISH showed intracerebral dissemination of P...
2017: Journal of Oral Microbiology
https://www.readbyqxmd.com/read/28324763/interaction-of-apoe-e4-and-poor-glycemic-control-predicts-white-matter-hyperintensity-growth-from-73-to-76
#12
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
#13
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
#14
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/28323160/effect-of-age-and-the-apoe-gene-on-metabolite-concentrations-in-the-posterior-cingulate-cortex
#15
Sana Suri, Uzay Emir, Charlotte J Stagg, Jamie Near, Ralf Mekle, Florian Schubert, Enikő Zsoldos, Abda Mahmood, Archana Singh-Manoux, Mika Kivimäki, Klaus P Ebmeier, Clare E Mackay, Nicola Filippini
Proton magnetic resonance spectroscopy ((1)H-MRS) has provided valuable information about the neurochemical profile of Alzheimer's disease (AD). However, its clinical utility has been limited in part by the lack of consistent information on how metabolite concentrations vary in the normal aging brain and in carriers of apolipoprotein E (APOE) ε4, an established risk gene for AD. We quantified metabolites within an 8cm(3) voxel within the posterior cingulate cortex (PCC)/precuneus in 30 younger (20-40 years) and 151 cognitively healthy older individuals (60-85 years)...
March 18, 2017: NeuroImage
https://www.readbyqxmd.com/read/28320424/the-alzheimer-s-disease-risk-factors-apolipoprotein-e-and-trem2-are-linked-in-a-receptor-signaling-pathway
#16
Charlotte Jendresen, Vibeke Årskog, Michael R Daws, Lars N G Nilsson
BACKGROUND: Triggering receptor expressed on myeloid cells 2 (TREM2) and apolipoprotein E (APOE) are genetically linked to Alzheimer's disease. Here, we investigated whether human ApoE mediates signal transduction through human and murine TREM2 and sought to identify a TREM2-binding domain in human ApoE. METHODS: To investigate cell signaling through TREM2, a cell line was used which expressed an NFAT-inducible β-galactosidase reporter and human or murine TREM2, fused to CD8 transmembrane and CD3ζ intracellular signaling domains...
March 21, 2017: Journal of Neuroinflammation
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
#17
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/28315714/cadmium-induced-malignant-transformation-of-rat-liver-cells-potential-key-role-and-regulatory-mechanism-of-altered-apolipoprotein-e-expression-in-enhanced-invasiveness
#18
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 16, 2017: Toxicology
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
#19
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/28302625/silencing-of-anticoagulant-protein-c-evokes-low-incident-but-spontaneous-atherothrombosis-in-apolipoprotein-e-deficient-mice
#20
Amber B Ouweneel, Marco Heestermans, Robin A F Verwilligen, Marion J J Gijbels, Pieter H Reitsma, Miranda van Eck, Bart J M van Vlijmen
OBJECTIVE: Murine atherosclerosis models do not spontaneously develop atherothrombotic complications. We investigated whether disruption of natural anticoagulation allows preexisting atherosclerotic plaques to progress toward an atherothrombotic phenotype. APPROACH AND RESULTS: On lowering of plasma protein C levels with small interfering RNA (siProc) in 8-week Western-type diet-fed atherosclerotic apolipoprotein E-deficient mice, one out of 4 mice displayed a large, organized, and fibrin- and leukocyte-rich thrombus on top of an advanced atherosclerotic plaque located in the aortic root...
March 16, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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