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Apolipoprotein E

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https://www.readbyqxmd.com/read/29161341/distinct-spatiotemporal-accumulation-of-n-truncated-and-full-length-amyloid-%C3%AE-42-in-alzheimer-s-disease
#1
Mitsuru Shinohara, Shunsuke Koga, Takuya Konno, Jeremy Nix, Motoko Shinohara, Naoya Aoki, Pritam Das, Joseph E Parisi, Ronald C Petersen, Terrone L Rosenberry, Dennis W Dickson, Guojun Bu
Accumulation of amyloid-β peptides is a dominant feature in the pathogenesis of Alzheimer's disease; however, it is not clear how individual amyloid-β species accumulate and affect other neuropathological and clinical features in the disease. Thus, we compared the accumulation of N-terminally truncated amyloid-β and full-length amyloid-β, depending on disease stage as well as brain area, and determined how these amyloid-β species respectively correlate with clinicopathological features of Alzheimer's disease...
November 17, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29159568/a-cross-sectional-and-longitudinal-study-between-association-of-n-3-polyunsaturated-fatty-acids-derived-from-fish-consumption-and-high-density-lipoprotein-heterogeneity
#2
Shigemasa Tani, Rei Matsuo, Kenji Kawauchi, Tsukasa Yagi, Wataru Atsumi, Atsushi Hirayama
Decreased high-density lipoprotein (HDL) particle size, cholesterol poor, apolipoprotein A-I-rich HDL particles leading to smaller HDL particle size, may be associated with an anti-atherosclerotic effect. The data are sparse regarding the relationship between n-3 polyunsaturated fatty acids [n-3 PUFAs: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)] and HDL particle size. This study was designed as a hospital-based cross-sectional study to investigate the relationship between the serum levels of n-3 PUFAs and the HDL-cholesterol/apolipoprotein A-1 ratio, as estimated by the HDL particle size, in patients with the presence of one or more risk factors for atherosclerotic cardiovascular disease (ASCVD)...
November 20, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/29159264/the-effects-of-apolipoprotein-e-genotype-%C3%AE-synuclein-deficiency-and-sex-on-brain-synaptic-and-alzheimer-s-disease-related-pathology
#3
Roni Bar, Anat Boehm-Cagan, Ishai Luz, Yarden Kleper-Wall, Daniel M Michaelson
Introduction: Alzheimer's disease (AD) and synucleinopathies share common pathological mechanisms. Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for AD, also increases the risk for dementia in pure synucleinopathies. We presently examined the effects of α-synuclein deficiency (α-syn-/-) and sex on apoE4-driven pathologies. Methods: AD-related, synaptic, and vascular markers were analyzed in female and male α-syn-/- and α-syn+/+ apoE4, apoE3, and apoE3/E4 mice...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29158532/recombinant-decorin-fusion-protein-attenuates-murine-abdominal-aortic-aneurysm-formation-and-rupture
#4
Yue Shen, Valerio Russo, Matthew R Zeglinski, Stephanie L Sellers, Zhengguo Wu, Cameron Oram, Stephanie Santacruz, Yulia Merkulova, Christopher Turner, Keerit Tauh, Hongyan Zhao, Tatjana Bozin, Lubos Bohunek, Haishan Zeng, Michael A Seidman, R Chris Bleackley, Bruce M McManus, Erkki Ruoslahti, Tero A H Järvinen, David J Granville
Decorin (DCN) is a small-leucine rich proteoglycan that mediates collagen fibrillogenesis, organization, and tensile strength. Adventitial DCN is reduced in abdominal aortic aneurysm (AAA) resulting in vessel wall instability thereby predisposing the vessel to rupture. Recombinant DCN fusion protein CAR-DCN was engineered with an extended C-terminus comprised of CAR homing peptide that recognizes inflamed blood vessels and penetrates deep into the vessel wall. In the present study, the role of systemically-administered CAR-DCN in AAA progression and rupture was assessed in a murine model...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29157655/roles-of-high-apolipoprotein-e-blood-levels-and-hdl-in-development-of-familial-dysbetalipoproteinemia-in-%C3%AE%C2%B52%C3%AE%C2%B52-subjects
#5
James P Corsetti, Charles E Sparks, Stephan J L Bakker, Eke G Gruppen, Robin P F Dullaart
OBJECTIVE: Familial dysbetalipoproteinemia (FD) or Type III hyperlipoproteinemia is a mixed hyperlipidemia closely associated with the ε2ε2 genotype of the common APOE polymorphism although not all homozygotes progress to FD. Unlike the polymorphism, few studies explore effects of apolipoprotein E (apoE) blood levels on FD development. Likewise, despite the known apoE2 lipoprotein binding preference for high-density lipoprotein (HDL); little work exists exploring HDL in FD. Accordingly, this study was undertaken to investigate potential roles in FD development for apoE and HDL...
November 17, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/29156223/exploring-apoe-genotype-effects-on-ad-risk-and-%C3%AE-amyloid-burden-in-individuals-with-subjective-cognitive-decline-the-facehbi-study-baseline-results
#6
Sonia Moreno-Grau, O Rodríguez-Gomez, A Sanabria, A Perez-Cordon, D Sanchez-Ruiz, C Abdelnour, S Valero, I Hernandez, M Rosende-Roca, A Mauleon, L Vargas, A Lafuente, S Gil, M A Santos-Santos, M Alegret, A Espinosa, G Ortega, M Guitart, A Gailhajanet, I de Rojas, O Sotolongo-Grau, S Ruiz, N Aguilera, J Papasey, E Martin, E Peleja, F Lomeña, F Campos, A Vivas, M Gomez-Chiari, M A Tejero, J Giménez, M Serrano-Ríos, A Orellana, L Tarraga, A Ruiz, M Boada
INTRODUCTION: Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. METHODS: We evaluated apolipoprotein E (APOE) Ɛ4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta-analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts...
November 17, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29156222/cerebral-small-vessel-disease-in-middle-age-and-genetic-predisposition-to-late-onset-alzheimer-s-disease
#7
James D Stefaniak, Li Su, Elijah Mak, Nasim Sheikh Bahaei, Katie Wells, Karen Ritchie, Adam Waldman, Craig W Ritchie, John T O'Brien
INTRODUCTION: Cerebral small vessel disease (CSVD) is associated with late-onset Alzheimer's disease (LOAD) and might contribute to the relationship between apolipoprotein E ε4 (APOEε4) and LOAD, in older people. However, it is unclear whether CSVD begins in middle age in individuals genetically predisposed to LOAD. METHODS: We assessed the relationship between radiological markers of CSVD, white matter hyperintensities and microbleeds, and genetic predisposition to LOAD in a cross-sectional analysis of cognitively normal subjects aged 40-59 years recruited from the PREVENT Dementia study...
November 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29155887/effects-of-an-a%C3%AE-antibody-fragment-on-a%C3%AE-aggregation-and-astrocytic-uptake-are-modulated-by-apolipoprotein-e-and-j-mimetic-peptides
#8
Laia Montoliu-Gaya, Sandra D Mulder, Robert Veerhuis, Sandra Villegas
Aβ-Immunotherapy has long been studied in the treatment of Alzheimer's disease (AD), but not how other molecules involved in the disease can affect antibody performance. We previously designed an antibody fragment, scFv-h3D6, and showed that it precludes Aβ-induced cytotoxicity by withdrawing Aβ oligomers from the amyloid pathway towards a non-toxic, worm-like pathway. ScFv-h3D6 was effective at the behavioral, cellular, and molecular levels in the 3xTg-AD mouse model. Because scFv-h3D6 treatment restored apolipoprotein E (apoE) and J (apoJ) concentrations to non-pathological values, and Aβ internalization by glial cells was found to be decreased in the presence of these apolipoproteins, we now aimed to test the influence of scFv-h3D6 on Aβ aggregation and cellular uptake by primary human astrocytes in the presence of therapeutic apoE and apoJ mimetic peptides (MPs)...
2017: PloS One
https://www.readbyqxmd.com/read/29155708/enrichment-of-detergent-insoluble-protein-aggregates-from-human-postmortem-brain
#9
Ian Diner, Tram Nguyen, Nicholas T Seyfried
In this study, we describe an abbreviated single-step fractionation protocol for the enrichment of detergent-insoluble protein aggregates from human postmortem brain. The ionic detergent N-lauryl-sarcosine (sarkosyl) effectively solubilizes natively folded proteins in brain tissue allowing the enrichment of detergent-insoluble protein aggregates from a wide range of neurodegenerative proteinopathies, such as Alzheimer's disease (AD), Parkinson's disease and amyotrophic lateral sclerosis, and prion diseases...
October 24, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29154926/site-specific-effects-of-apolipoprotein-e-expression-on-diet-induced-obesity-and-white-adipose-tissue-metabolic-activation
#10
Aikaterini Hatziri, Christina Kalogeropoulou, Eva Xepapadaki, Eleni Birli, Eleni A Karavia, Eugenia Papakosta, Serafoula Filou, Caterina Constantinou, Kyriakos E Kypreos
Apolipoprotein E (APOE) has been strongly implicated in the development of diet induced obesity. In the present study, we investigated the contribution of brain and peripherally expressed human apolipoprotein E3 (APOE3), the most common human isoform, to diet induced obesity. In our studies APOE3 knock-in (Apoe3(knock-in)), Apoe-deficient (apoe(-/-)) and brain-specific expressing APOE3 (Apoe3(brain)) mice were fed western-type diet for 12week and biochemical analyses were performed. Moreover, AAV-mediated gene transfer of APOE3 to apoe(-/-) mice was employed, as a means to achieve APOE3 expression selectively in periphery, since peripherally expressed APOE does not cross barrier (BBB) or blood-cerebrospinal fluid barrier (BCSFB)...
November 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29154780/the-feedback-loop-of-emmprin-nf-%C3%AE%C2%BAb-worsens-atherosclerotic-plaque-via-suppressing-autophagy-in-macrophage
#11
Xing Liang, Xianhua Hou, Yang Yang, Hong Liu, Ruiwei Guo, Zhihua Yang, Lixia Yang
This study examined the significance of macrophage autophagy in extracellular matrix metalloproteinase inducer (EMMPRIN)-mediated atherosclerosis (AS). Apolipoprotein E-deficient (ApoE-/-) mice were fed a western diet to establish an AS model. EMMPRIN and p62/Sequestosome-1(SQSTM1) expression were evaluated in plaque macrophages from the AS mice using immunofluorescence. The EMMPRIN and p62/SQSTM1 protein expression levels in macrophages increased with the increasing vulnerability of the atherosclerotic plaques...
November 14, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29152896/trimetazidine-restores-the-positive-adaptation-to-exercise-training-by-mitigating-statin-induced-skeletal-muscle-injury
#12
Ming Song, Fang-Fang Chen, Yi-Hui Li, Lei Zhang, Feng Wang, Ran-Ran Qin, Zhi-Hao Wang, Ming Zhong, Meng-Xiong Tang, Wei Zhang, Lu Han
BACKGROUND: Exercise rehabilitation is demonstrated to improve the prognosis of patients with coronary heart disease (CHD). Statins, as the key medicine to lower cholesterol in CHD, result in skeletal muscle injury and impair exercise training adaptation. Energy metabolism dysfunction is identified as the potential mechanism underlying statin-induced skeletal muscle injury. In this study, we investigated the effects of the metabolic modulator trimetazidine on skeletal muscle energy metabolism and statin-associated exercise intolerance...
November 19, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29143599/epistasis-physical-capacity-related-genes-and-exceptional-longevity-fndc5-gene-interactions-with-candidate-genes-foxoa3-and-apoe
#13
Noriyuki Fuku, Roberto Díaz-Peña, Yasumichi Arai, Yukiko Abe, Hirofumi Zempo, Hisashi Naito, Haruka Murakami, Motohiko Miyachi, Carlos Spuch, José A Serra-Rexach, Enzo Emanuele, Nobuyoshi Hirose, Alejandro Lucia
BACKGROUND: Forkhead box O3A (FOXOA3) and apolipoprotein E (APOE) are arguably the strongest gene candidates to influence human exceptional longevity (EL, i.e., being a centenarian), but inconsistency exists among cohorts. Epistasis, defined as the effect of one locus being dependent on the presence of 'modifier genes', may contribute to explain the missing heritability of complex phenotypes such as EL. We assessed the potential association of epistasis among candidate polymorphisms related to physical capacity, as well as antioxidant defense and cardiometabolic traits, and EL in the Japanese population...
November 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29143217/fluid-biomarker-agreement-and-interrelation-in-dementia-due-to-alzheimer-s-disease
#14
Panagiotis Alexopoulos, Jennifer Roesler, Lukas Werle, Nathalie Thierjung, Iliana Lentzari, Marion Ortner, Timo Grimmer, Nikolaos Laskaris, Antonios Politis, Philippos Gourzis, Alexander Kurz, Robert Perneczky
The cerebrospinal fluid (CSF) levels of β-amyloid 42, total tau, and phosphorylated tau 181 are supposed to be all continuously abnormal in dementia due to Alzheimer's disease (AD), being the most advanced disease stage. The aim of the present study, which included a monocentric and a multicentric sample (N = 119 and 178, respectively), was to investigate the degree of CSF biomarker agreement and interrelation in AD dementia. Based on previously published cut-off values, biomarker values were categorized as positive or negative for AD (dichotomization strategy) and as either positive, negative, or borderline (trichotomization strategy)...
November 15, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29141139/the-effect-of-synthetic-high-density-lipoproteins-modification-with-polyethylene-glycol-on-pharmacokinetics-and-pharmacodynamics
#15
Dan Li, Maria V Fawaz, Emily E Morin, Ran Ming, Denis Sviridov, Jie Tang, Rose Ackerman, Karl Olsen, Alan T Remaley, Anna Schwendeman
Synthetic high density lipoprotein nanoparticles (sHDL) capable of mobilizing excess cholesterol from atherosclerotic arteries and delivering it to the liver for elimination have been shown to reduce plaque burden in patients. Unfortunately, sHDLs have a narrow therapeutic index and relative to the endogenous HDL shorter circulation half-life. Surface modification with polyethylene glycol (PEG) was investigated for its potential to extend sHDL circulation in vivo. Various amounts (2.5, 5 and 10%) and different chain lengths (2 and 5 kDa) of PEG-modified lipids were incorporated in sHDL's lipid membrane...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29133888/neuronal-hyperactivity-due-to-loss-of-inhibitory-tone-in-apoe4-mice-lacking-alzheimer-s-disease-like-pathology
#16
Tal Nuriel, Sergio L Angulo, Usman Khan, Archana Ashok, Qiuying Chen, Helen Y Figueroa, Sheina Emrani, Li Liu, Mathieu Herman, Geoffrey Barrett, Valerie Savage, Luna Buitrago, Efrain Cepeda-Prado, Christine Fung, Eliana Goldberg, Steven S Gross, S Abid Hussaini, Herman Moreno, Scott A Small, Karen E Duff
The ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer's disease (AD). However, the reason APOE4 is associated with increased AD risk remains a source of debate. Neuronal hyperactivity is an early phenotype in both AD mouse models and in human AD, which may play a direct role in the pathogenesis of the disease. Here, we have identified an APOE4-associated hyperactivity phenotype in the brains of aged APOE mice using four complimentary techniques-fMRI, in vitro electrophysiology, in vivo electrophysiology, and metabolomics-with the most prominent hyperactivity occurring in the entorhinal cortex...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29131706/alzheimer-s-disease-current-status-and-future-directions
#17
Deepshikha Bhardwaj, Connie Mitra, Chandrakala Aluganti Narasimhulu, Aladdin Riad, Mitsushita Doomra, Sampath Parthasarathy
Alzheimer's disease (AD) is an age-related neurodegenerative disorder of the brain. The presence of amyloid-beta (Aβ) plaques, neurofibrillary tangles (NFTs), loss of neurons, synapses, and altered sensory perceptions, including memory loss, delineate AD. However, the cause of AD is not clearly known. Several genetic and nongenetic factors have been implicated in the disease. Of the genes, the ɛ4 allele of apolipoprotein E is the largest known genetic risk factor of AD. This review article focuses on the various genetic and other predisposing factors that account for AD, pathophysiology of the disease, and the mechanisms by which Aβ plaques and NFTs are formed and could affect AD brain...
November 13, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29128402/an-anti-inflammatory-chalcone-derivative-prevents-heart-and-kidney-from-hyperlipidemia-induced-injuries-by-attenuating-inflammation
#18
Xiong Chen, Weihui Yu, Weixin Li, Hailing Zhang, Weijian Huang, Jingying Wang, Weiwei Zhu, Qilu Fang, Chao Chen, Xiaokun Li, Guang Liang
Obesity is a growing pandemic in both developed and developing countries. Lipid overload in obesity generates a chronic, low-grade inflammation state. Increased inflammation in heart and renal tissues has been shown to promote the progression of heart and renal damage in obesity. Previously, we found that a novel chalcone derivative, L6H21, inhibited lipopolysaccharide-induced inflammatory response. In the present study, we investigated the effects of L6H21 on inflammatory responses in culture and in animal models of lipid overload...
November 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29124110/characterization-of-apoe-and-tomm40-allele-frequencies-in-the-japanese-population
#19
Akira Nishimura, Hidenori Nonomura, Shingo Tanaka, Michihiro Yoshida, Yuka Maruyama, Yutaka Aritomi, Ann M Saunders, Daniel K Burns, Michael W Lutz, Grant Runyan, Eric Lai, Kumar Budur, Allen D Roses
Introduction: Dementia is one of the major health threats to our aging society, and Alzheimer's disease (AD) is the leading cause. In Japan, ∼15% of the elderly population has dementia. The apolipoprotein E (APOE) genotype and a polymorphism (rs10524523) in the translocase of outer mitochondrial membrane 40 (TOMM40) gene have been associated with the age of onset of AD. However, differences in allele frequencies of these markers in different ethnic populations are not well known. Methods: Whole blood samples were collected from 300 Japanese subjects, and genomic DNA was extracted to determine APOE alleles and TOMM40 rs10524523 genotypes...
November 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/29123261/a-new-panel-of-pancreatic-cancer-biomarkers-discovered-using-a-mass-spectrometry-based-pipeline
#20
Xiaohui Liu, Weimin Zheng, Wansheng Wang, Huali Shen, Linxiao Liu, Wenhui Lou, Xiaolin Wang, Pengyuan Yang
BACKGROUND: Pancreatic carcinoma (PC) is an aggressive malignancy that lacks strategies for early detection. This study aimed to develop a coherent, high-throughput and non-discriminatory pipeline for the novel clinical biomarker discovery of PC. METHODS: We combined mass spectrometry (MS)-intensive methods such as isobaric tags for relative and absolute quantitation with two-dimensional liquid chromatography-tandem mass spectrometry (iTRAQ-2DLC-MS/MS), 1D-targeted LC-MS/MS, prime MRM (P-MRM) and stable isotope dilution-based MRM (SID-MRM) to analyse serum samples from healthy people (normal control, NC), patients with benign diseases (BD) and PC patients to identify novel biomarkers of PC...
November 9, 2017: British Journal of Cancer
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