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Apo E4

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https://www.readbyqxmd.com/read/28731446/effect-of-apoe-genotype-on-synaptic-proteins-in-earlier-adult-life
#1
Lindsey I Sinclair, Seth Love
BACKGROUND: Possession of APOEɛ4 is a strong risk factor for late-onset Alzheimer's disease and is associated with loss of synaptic proteins in the elderly even in the absence of Alzheimer's disease. OBJECTIVE: We hypothesized that ɛ4 allele possession in non-demented adults aged under-75 would also be associated with alterations in the levels of synaptic proteins. METHODS: We measured synaptophysin, PSD95, drebrin, SNAP-25, and septin 7 by ELISA in hippocampus and superior temporal gyrus from 103 adults aged <75 without dementia...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731444/the-relationship-of-brain-amyloid-load-and-apoe-status-to-regional-cortical-thinning-and-cognition-in-the-adni-cohort
#2
Chunfei Li, David A Loewenstein, Ranjan Duara, Mercedes Cabrerizo, Warren Barker, Malek Adjouadi
BACKGROUND: Both amyloid (Aβ) load and APOE4 allele are associated with neurodegenerative changes in Alzheimer's disease (AD) prone regions and with risk for cognitive impairment. OBJECTIVE: To evaluate the unique and independent contribution of APOE4 allele status (E4+∖E4-), Aβ status (Amy+∖Amy-), and combined APOE4 and Aβ status on regional cortical thickness (CoTh) and cognition among participants diagnosed as cognitively normal (CN, n = 251), early mild cognitive impairment (EMCI, n = 207), late mild cognitive impairment (LMCI, n = 196), and mild AD (n = 162) from the ADNI...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731260/transcriptional-regulation-of-app-by-apoe-to-boldly-go-where-no-isoform-has-gone-before-apoe-app-transcription-and-ad-hypothesised-mechanisms-and-existing-knowledge-gaps
#3
REVIEW
Liying Corinne Lee, Michele Q L Goh, Edward H Koo
Alzheimer's disease (AD) is the most common form of dementia that gradually disrupts the brain network to impair memory, language and cognition. While the amyloid hypothesis remains the leading proposed mechanism to explain AD pathophysiology, anti-amyloid therapeutic strategies have yet to translate into useful therapies, suggesting that amyloid β-protein and its precursor, the amyloid precursor protein (APP) are but a part of the disease cascade. Further, risk of AD can be modulated by a number of factors, the most impactful being the ɛ4 isoform of apolipoprotein E (apoE)...
July 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28726810/a-randomized-controlled-trial-of-disclosing-genetic-risk-information-for-alzheimer-disease-via-telephone
#4
Kurt D Christensen, Wendy R Uhlmann, J Scott Roberts, Erin Linnenbringer, Peter J Whitehouse, Charmaine D M Royal, Thomas O Obisesan, L Adrienne Cupples, Melissa B Butson, Grace-Ann Fasaye, Susan Hiraki, Clara A Chen, Uwe Siebert, Robert Cook-Deegan, Robert C Green
PurposeTelephone disclosure of genetic test results can improve access to services. To date, studies of its impact have focused on return of Mendelian risk information, principally hereditary cancer syndromes.MethodsIn a multisite trial of Alzheimer disease genetic risk disclosure, asymptomatic adults were randomized to receive test results in person or via telephone. Primary analyses examined patient outcomes 12 months after disclosure.ResultsData from 257 participants showed that telephone disclosure occurred 7...
July 20, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28707482/peripheral-inflammation-apolipoprotein-e4-and-amyloid-%C3%AE-interact-to-induce-cognitive-and-cerebrovascular-dysfunction
#5
Felecia M Marottoli, Yuriko Katsumata, Kevin P Koster, Riya Thomas, David W Fardo, Leon M Tai
Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer's disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 ( APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated. The goal of this study was to determine the interactive effect of APOE4, Aβ, and chronic repeated peripheral inflammation on cerebrovascular and cognitive dysfunction in vivo...
July 2017: ASN Neuro
https://www.readbyqxmd.com/read/28705029/bosnian-study-of-apoe-distribution-bosad-a-comparison-with-other-european-populations
#6
Grażyna Adler, Mateusz A Adler, Anna Urbańska, Karolina Skonieczna-Żydecka, Emina Kiseljakovic, Amina Valjevac, Miłosz Parczewski, Almira Hadzovic-Dzuvo
BACKGROUND: The ε2, ε3 and ε4 alleles of APOE gene have been associated with several diseases in different populations. Data on the frequency of alleles are used in both a clinical and evolutionary context. Although the data on frequency of these alleles are numerous, there are no reports for the population of Bosnia and Herzegovina. AIM: To estimate the frequency of APOE alleles in a healthy Bosnian population and compare it to data for other European populations...
July 13, 2017: Annals of Human Biology
https://www.readbyqxmd.com/read/28684412/isoform-and-cell-type-specific-structure-of-apolipoprotein-e-lipoparticles-as-revealed-by-a-novel-forster-resonance-energy-transfer-assay
#7
Eleanna Kara, Jordan D Marks, Zhanyun Fan, Jacob A Klickstein, Allyson D Roe, Kelly A Krogh, Susanne Wegmann, Masato Maesako, Christina C Luo, Ravi Mylvaganam, Oksana Berezovska, Eloise Hudry, Bradley T Hyman
Apolipoprotein E (ApoE) has an important role in the pathogenesis of Alzheimer's disease with its three isoforms having distinct effects on disease risk. Here, we assessed the conformational differences between those isoforms using a novel flow cytometry-Forster Resonance Energy Transfer (FRET) assay. We showed that the conformation of intracellular ApoE within HEK cells and astrocytes adopts a directional pattern; in other words, E4 adopts the most closed conformation, E2 the most open conformation, and E3 an intermediate conformation...
July 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28670684/apolipoprotein-e-polymorphism-and-left-ventricular-failure-in-beta-thalassemia-a-multivariate-meta-analysis
#8
Niki L Dimou, Katerina G Pantavou, Pantelis G Bagos
Apolipoprotein E (ApoE) is potentially a genetic risk factor for the development of left ventricular failure (LVF), the main cause of death in beta-thalassemia homozygotes. In the present study, we synthesize the results of independent studies examining the effect of ApoE on LVF development in thalassemic patients through a meta-analytic approach. However, all studies report more than one outcome, as patients are classified into three groups according to the severity of the symptoms and the genetic polymorphism...
July 2, 2017: Annals of Human Genetics
https://www.readbyqxmd.com/read/28659481/hepatitis-c-virus-strain-dependent-usage-of-apolipoprotein-e-modulates-assembly-efficiency-and-specific-infectivity-of-secreted-virions
#9
Romy Weller, Kathrin Hueging, Richard J P Brown, Daniel Todt, Sebastian Joecks, Florian W R Vondran, Thomas Pietschmann
Hepatitis C virus (HCV) is extraordinarily diverse and uses entry factors in a strain-specific manner. Virus particles associate with lipoproteins and Apolipoprotein E (ApoE) is critical for HCV assembly and infectivity. However, whether ApoE-dependency is common to all HCV genotypes remains unknown. Therefore, we compared the role of ApoE utilizing ten virus strains from genotypes 1 through 7. ApoA and ApoC also support HCV assembly, so they may contribute to virus production in a strain-dependent fashion...
June 28, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28648916/long-term-changes-in-time-spent-walking-and-subsequent-cognitive-and-structural-brain-changes-in-older-adults
#10
John R Best, Caterina Rosano, Howard J Aizenstein, Qu Tian, Robert M Boudreau, Hilsa N Ayonayon, Suzanne Satterfield, Eleanor M Simonsick, Stephanie Studenski, Kristine Yaffe, Teresa Liu-Ambrose
Previous studies have shown that more active older adults have better cognition and brain health based on a variety of structural neuroimaging measures. Nevertheless, the effects of maintaining physical activity (PA) over an extended period of time on future changes in older adults' cognition and brain structure are unknown. Participants were 141 initially well-functioning community-dwelling older adults (aged 70-79 years at baseline; 60% female; 42% black) studied over a 13-year period. PA (self-reported time spent walking) was assessed annually from years 1 to 10...
June 6, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28634550/sortilin-related-receptor-expression-in-human-neural-stem-cells-derived-from-alzheimer-s-disease-patients-carrying-the-apoe-epsilon-4-allele
#11
Alen Zollo, Zoe Allen, Helle F Rasmussen, Filomena Iannuzzi, Yichen Shi, Agnete Larsen, Thorsten J Maier, Carmela Matrone
Alzheimer's disease (AD) is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4) allele. Changes in amyloid precursor protein (APP) binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ) peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1) as an important factor in APP trafficking and processing...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28634213/omega-3-fatty-acids-increase-the-unfolded-protein-response-and-improve-amyloid-%C3%AE-phagocytosis-by-macrophages-of-patients-with-mild-cognitive-impairment
#12
Henry M Olivera-Perez, Larry Lam, Johnny Dang, Weilan Jiang, Fabian Rodriguez, Elizabeth Rigali, Sarah Weitzman, Verna Porter, Liudmilla Rubi, Marco Morselli, Matteo Pellegrini, Milan Fiala
Mϕs of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ. ω-3 in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI. Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1...
June 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28614836/visual-evaluation-of-medial-temporal-lobe-atrophy-as-a-clinical-marker-of-conversion-from-mild-cognitive-impairment-to-dementia-and-for-predicting-progression-in-patients-with-mild-cognitive-impairment-and-mild-alzheimer-s-disease
#13
Karin Persson, Maria Lage Barca, Rannveig Sakshaug Eldholm, Lena Cavallin, Jūratė Šaltytė Benth, Geir Selbæk, Anne Brækhus, Ingvild Saltvedt, Knut Engedal
BACKGROUND/AIMS: To evaluate whether visual assessment of medial temporal lobe atrophy (vaMTA) can predict 2-year conversion from mild cognitive impairment (MCI) to dementia and progression of MCI and Alzheimer's disease dementia as measured by the Clinical Dementia Rating Scale Sum of Boxes score (CDR-SB). METHODS: vaMTA was performed in 94 patients with MCI according to the Winblad criteria and in 124 patients with AD according to ICD-10 and NINCDS-ADRDA criteria...
June 15, 2017: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/28597004/increased-binding-of-apolipoproteins-a-i-and-e4-to-triglyceride-rich-lipoproteins-is-linked-to-induction-of-hypertriglyceridemia
#14
Irina N Gorshkova, David Atkinson
Hypertriglyceridemia (HTG) is an independent factor of atherosclerotic cardiovascular disease and a hallmark of many metabolic disorders. However, the molecular etiology of HTG is still largely unknown. In mice, severe HTG may be induced by expression of specific mutants of apolipoprotein (apo) A-I or wild type (WT) apoE4. Expression of a certain apoE4 mutant results in mild HTG, while expression of another apoE4 mutant or WT apoA-I results in normal plasma triglyceride (TG) levels. Biophysical studies of the apoA-I and apoE4 forms associated with HTG help better understand the molecular mechanisms of induction of HTG by these proteins...
2017: JSM Atheroscler
https://www.readbyqxmd.com/read/28596117/disrupted-white-matter-structural-networks-in-healthy-older-adult-apoe-%C3%AE%C2%B54-carriers-an-international-multicenter-dti-study
#15
Enrica Cavedo, Simone Lista, Katrine Rojkova, Patrizia A Chiesa, Marion Houot, Katharina Brueggen, Janusch Blautzik, Arun L W Bokde, Bruno Dubois, Frederik Barkhof, Petra J W Pouwels, Stefan Teipel, Harald Hampel
The ε4 allelic variant of the Apolipoprotein E gene (APOE ε4) is the best-established genetic risk factor for late-onset Alzheimer's disease (AD). White matter (WM) microstructural damages measured with Diffusion Tensor Imaging (DTI) represent an early sign of fiber tract disconnection in AD. We examined the impact of APOE ε4 on WM microstructure in elderly individuals from the multicenter European DTI Study on Dementia. Voxelwise statistical analysis of fractional anisotropy (FA), mean diffusivity, radial and axial diffusivity (MD, radD and axD respectively) was carried out using Tract-Based Spatial Statistics...
June 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28582863/framingham-risk-score-and-the-risk-of-progression-from-mild-cognitive-impairment-to-dementia
#16
Giovanna Viticchi, Lorenzo Falsetti, Laura Buratti, Giulia Sajeva, Simona Luzzi, Marco Bartolini, Leandro Provinciali, Mauro Silvestrini
BACKGROUND: Mild cognitive impairment (MCI) often represents the clinical manifestation of cognitive deterioration preceding Alzheimer's disease (AD). Currently, there are no reliable approaches for an objective evaluation of the risk of developing AD in MCI patients. OBJECTIVE: The aim of this study was to verify whether the Framingham cardiovascular risk profile (FCRP) could be useful to identify patients at the highest risk of conversion from MCI to AD. METHODS: Patients with amnestic MCI (aMCI) were carefully investigated to assess their vascular risk profile...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28578665/risk-factors-for-dementia-in-the-ninth-decade-of-life-and-beyond-a-study-of-the-lothian-birth-cohort-1921
#17
Ruth A Sibbett, Tom C Russ, Ian J Deary, John M Starr
BACKGROUND: With increasing numbers of people surviving beyond eighty years, this section of the population demands attention to reduce the impact of dementia. In order to develop effective preventative strategies, it is essential to understand age-specific risk factor profiles for dementia: do risk factors for dementia in those in their sixties and seventies persist into oldest age? The aims of this study were to determine incident dementia and to investigate the risk profile for dementia from age 79 to 95 years in a well-characterised cohort...
June 2, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28569173/apoe-isoforms-differentially-regulates-cleavage-and-secretion-of-bdnf
#18
Abhik Sen, Thomas J Nelson, Daniel L Alkon
Apolipoprotein E4 (ApoE4) is a major genetic risk factor for sporadic or late onset Alzheimer's disease (AD). Brain-derived neurotrophic factor (BDNF) is decreased by 3 to 4-fold in the brains of AD patients at autopsy. ApoE4 mice also have reduced BDNF levels. However, there have been no reports relating the different ApoE isoforms or AD to differential regulation of BDNF. Here we report that in the hippocampal regions of AD patients both prepro-BDNF and pro-BDNF expression showed a 40 and 60% decrease respectively compared to that expression in the hippocampi of age-matched control patients...
June 1, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28550258/effect-of-apoe-genotype-on-amyloid-deposition-brain-volume-and-memory-in-cognitively-normal-older-individuals
#19
Yen Ying Lim, Robert Williamson, Simon M Laws, Victor L Villemagne, Pierrick Bourgeat, Christopher Fowler, Stephanie Rainey-Smith, Olivier Salvado, Ralph N Martins, Christopher C Rowe, Colin L Masters, Paul Maruff
BACKGROUND: The association between the apolipoprotein E (APOE) ɛ4 allele and high risk of developing Alzheimer's disease (AD) dementia before the age of 80 has been recognized for over 30 years. However, the timing and mode of action of APOE is not understood, nor has there been a detailed analysis of the effect of APOE genotype on memory, hippocampal volume, and amyloid-β (Aβ) levels in cognitively normal adults. OBJECTIVE: Examine the effect of APOE allelic genotype on the relationship between Aβ levels, hippocampal volume, and memory in cognitively normal adults...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550244/apoe-%C3%AE%C2%B54-modulation-of-training-outcomes-in-several-cognitive-domains-in-a-sample-of-cognitively-intact-older-adults
#20
Ramón López-Higes, Inmaculada C Rodríguez-Rojo, José M Prados, Pedro Montejo, David Del-Río, María Luisa Delgado-Losada, Mercedes Montenegro, David López-Sanz, Ana Barabash
BACKGROUND: Most research points to the ɛ4 allele of the apolipoprotein E (APOE) gene as the most recognizable genetic risk factor associated with Alzheimer's disease pathogenesis. It has been also suggested that the APOEɛ4 allele has a negative influence on cognitive functioning, which begins long before cognitive impairment becomes manifest. However, still, little is known about the APOEɛ4 interaction with cognitive intervention programs. OBJECTIVE: The main goal of this study was to explore whether there was a differential APOE genotype modulation effect after cognitive training in different domains, such as language comprehension, executive functions, and memory...
2017: Journal of Alzheimer's Disease: JAD
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