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Apo E4

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https://www.readbyqxmd.com/read/28220068/reduced-activity-in-the-right-inferior-frontal-gyrus-in-elderly-apoe-e4-carriers-during-a-verbal-fluency-task
#1
Andrea Katzorke, Julia B M Zeller, Laura D Müller, Martin Lauer, Thomas Polak, Andreas Reif, Jürgen Deckert, Martin J Herrmann
Apolipoprotein-E4 (APOE-E4) is a major genetic risk factor for developing Alzheimer's disease (AD). The verbal fluency task (VFT), especially the subtask category fluency, has shown to provide a good discrimination between cognitively normal controls and subjects with AD. Interestingly, APOE-E4 seems to have no effect on the behavioral performance during a VFT in healthy elderly. Thus, the purpose of the present study was to reveal possible compensation mechanisms by investigating the effect of APOE-E4 on the hemodynamic response in non-demented elderly during a VFT by using functional near-infrared spectroscopy (fNIRS)...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28211809/the-methylenetetrahydrofolate-reductase-c677t-polymorphism-and-risk-for-late-onset-alzheimer-s-disease-further-evidence-in-an-italian-multicenter-study
#2
Andrea Stoccoro, Pierpaola Tannorella, Maria Grazia Salluzzo, Raffaele Ferri, Corrado Romano, Benedetta Nacmias, Gabriele Siciliano, Lucia Migliore, Fabio Coppedè
BACKGROUND: A functional polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, namely C677T (rs1801133), results in increased Hcy levels and has been associated with risk of late-onset Alzheimer's disease (LOAD). Many investigators reported association between rs1801133 and LOAD risk in Asian populations and in carriers of the apolipoprotein E (APOE) ɛ4 allele, but recent meta-analyses suggest a contribution also in other populations, including Caucasians and/or northern Africans...
February 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28183528/transethnic-genome-wide-scan-identifies-novel-alzheimer-s-disease-loci
#3
Gyungah R Jun, Jaeyoon Chung, Jesse Mez, Robert Barber, Gary W Beecham, David A Bennett, Joseph D Buxbaum, Goldie S Byrd, Minerva M Carrasquillo, Paul K Crane, Carlos Cruchaga, Philip De Jager, Nilufer Ertekin-Taner, Denis Evans, M Danielle Fallin, Tatiana M Foroud, Robert P Friedland, Alison M Goate, Neill R Graff-Radford, Hugh Hendrie, Kathleen S Hall, Kara L Hamilton-Nelson, Rivka Inzelberg, M Ilyas Kamboh, John S K Kauwe, Walter A Kukull, Brian W Kunkle, Ryozo Kuwano, Eric B Larson, Mark W Logue, Jennifer J Manly, Eden R Martin, Thomas J Montine, Shubhabrata Mukherjee, Adam Naj, Eric M Reiman, Christiane Reitz, Richard Sherva, Peter H St George-Hyslop, Timothy Thornton, Steven G Younkin, Badri N Vardarajan, Li-San Wang, Jens R Wendlund, Ashley R Winslow, Jonathan Haines, Richard Mayeux, Margaret A Pericak-Vance, Gerard Schellenberg, Kathryn L Lunetta, Lindsay A Farrer
BACKGROUND: Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. METHODS: We conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset...
February 6, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28164769/change-in-insr-apba2-and-ide-gene-expressions-in-brains-of-alzheimer%C3%A2-s-disease-patients
#4
Isabela Bazzo Da Costa, Roger Willian De Labio, Lucas Trevizani Rasmussen, Gustavo Arruda Viani, Elizabeth Chen, João Villares, Gustavo Turecki, Marília De Arruda Cardoso Smith, Spencer L M Payão
Alzheimer's disease (AD) is defined as a progressive and irreversible neurodegenerative disorder, the onset of which is mainly characterized by decreased cognition, memory loss, and mental confusion. This study sought to quantify mRNA expression of the APBA2, INSR and IDE genes in brain samples from both patients with AD and controls. We investigated the mRNA expression of the APBA2, INSR and IDE genes in 150 RNA samples from the entorhinal cortex, the auditory cortex, and the hippocampus of individuals with AD and elderly controls using real time PCR...
February 2, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28157104/a-multi-cohort-study-of-apoe-%C3%A9-4-and-amyloid-%C3%AE-effects-on-the-hippocampus-in-alzheimer-s-disease
#5
Wasim Khan, Vincent Giampietro, Tobias Banaschewski, Gareth J Barker, Arun L W Bokde, Christian Büchel, Patricia Conrod, Herta Flor, Vincent Frouin, Hugh Garavan, Penny Gowland, Anreas Heinz, Bernd Ittermann, Hervé Lemaître, Frauke Nees, Tomas Paus, Zdenka Pausova, Marcella Rietschel, Michael N Smolka, Andreas Ströhle, Jeurgen Gallinat, Bruno Vellas, Hilkka Soininen, Iwona Kloszewska, Magda Tsolaki, Patrizia Mecocci, Christian Spenger, Victor L Villemagne, Colin L Masters, J-Sebastian Muehlboeck, Lars Bäckman, Laura Fratiglioni, Grégoria Kalpouzos, Lars-Olof Wahlund, Gunther Schumann, Simon Lovestone, Steven C R Williams, Eric Westman, Andrew Simmons
The apolipoprotein E (APOE) gene has been consistently shown to modulate the risk of Alzheimer's disease (AD). Here, using an AD and normal aging dataset primarily consisting of three AD multi-center studies (n = 1,781), we compared the effect of APOE and amyloid-β (Aβ) on baseline hippocampal volumes in AD patients, mild cognitive impairment (MCI) subjects, and healthy controls. A large sample of healthy adolescents (n = 1,387) was also used to compared hippocampal volumes between APOE groups. Subjects had undergone a magnetic resonance imaging (MRI) scan and APOE genotyping...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28140404/particulate-air-pollutants-apoe-alleles-and-their-contributions-to-cognitive-impairment-in-older-women-and-to-amyloidogenesis-in-experimental-models
#6
M Cacciottolo, X Wang, I Driscoll, N Woodward, A Saffari, J Reyes, M L Serre, W Vizuete, C Sioutas, T E Morgan, M Gatz, H C Chui, S A Shumaker, S M Resnick, M A Espeland, C E Finch, J C Chen
Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer's disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women's Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers...
January 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28135351/association-between-mentally-stimulating-activities-in-late-life-and-the-outcome-of-incident-mild-cognitive-impairment-with-an-analysis-of-the-apoe-%C3%AE%C2%B54-genotype
#7
Janina Krell-Roesch, Prashanthi Vemuri, Anna Pink, Rosebud O Roberts, Gorazd B Stokin, Michelle M Mielke, Teresa J H Christianson, David S Knopman, Ronald C Petersen, Walter K Kremers, Yonas E Geda
Importance: Cross-sectional associations between engagement in mentally stimulating activities and decreased odds of having mild cognitive impairment (MCI) or Alzheimer disease have been reported. However, little is known about the longitudinal outcome of incident MCI as predicted by late-life (aged ≥70 years) mentally stimulating activities. Objectives: To test the hypothesis of an association between mentally stimulating activities in late life and the risk of incident MCI and to evaluate the influence of the apolipoprotein E (APOE) ε4 genotype...
January 30, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28106546/a-common-variant-of-il-6r-is-associated-with-elevated-il-6-pathway-activity-in-alzheimer-s-disease-brains
#8
Patrick C G Haddick, Jessica L Larson, Nisha Rathore, Tushar R Bhangale, Qui T Phung, Karpagam Srinivasan, David V Hansen, Jennie R Lill, Margaret A Pericak-Vance, Jonathan Haines, Lindsay A Farrer, John S Kauwe, Gerard D Schellenberg, Carlos Cruchaga, Alison M Goate, Timothy W Behrens, Ryan J Watts, Robert R Graham, Joshua S Kaminker, Marcel van der Brug
The common p.D358A variant (rs2228145) in IL-6R is associated with risk for multiple diseases and with increased levels of soluble IL-6R in the periphery and central nervous system (CNS). Here, we show that the p.D358A allele leads to increased proteolysis of membrane bound IL-6R and demonstrate that IL-6R peptides with A358 are more susceptible to cleavage by ADAM10 and ADAM17. IL-6 responsive genes were identified in primary astrocytes and microglia and an IL-6 gene signature was increased in the CNS of late onset Alzheimer's disease subjects in an IL6R allele dependent manner...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28103200/depressive-symptoms-influence-global-cognitive-impairment-indirectly-by-reducing-memory-and-executive-function-in-patients-with-mild-cognitive-impairment
#9
Chathuri Yatawara, Levinia Lim, Russell Chander, Juan Zhou, Nagaendran Kandiah
BACKGROUND: Depressive symptoms negatively influence global cognition in the elderly; however, the mechanism of this effect remains unclear. OBJECTIVE: To investigate whether depressive symptoms influence global cognitive function in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) by impeding specific neuropsychological abilities and under what conditions this effect might occur. METHOD: A sample of 259 participants (104 cognitively normal elderly controls, 66 patients with MCI and 89 patients with mild AD) underwent a comprehensive neuropsychological assessment...
December 2016: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28099631/associations-of-cerebrovascular-metabolism-genotypes-with-neuropsychiatric-symptoms-and-age-at-onset-of-alzheimer-s-disease-dementia
#10
Fabricio F de Oliveira, Elizabeth S Chen, Marilia C Smith, Paulo H Bertolucci
Objective: To study associations of cerebrovascular metabolism genotypes and haplotypes with age at Alzheimer's disease dementia (AD) onset and with neuropsychiatric symptoms according to each dementia stage. Methods: Consecutive outpatients with late-onset AD were assessed for age at dementia onset and Neuropsychiatric Inventory scores according to Clinical Dementia Rating scores, apolipoprotein E gene (APOE) haplotypes, angiotensin-converting enzyme gene (ACE) variants rs1800764 and rs4291, low-density lipoprotein cholesterol receptor gene (LDLR) variants rs11669576 and rs5930, cholesteryl ester transfer protein gene (CETP) variants I422V and TaqIB, and liver X receptor beta gene (NR1H2) polymorphism rs2695121...
January 12, 2017: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/28096372/helical-structure-stability-and-dynamics-in-human-apolipoprotein-e3-and-e4-by-hydrogen-exchange-and-mass-spectrometry
#11
Palaniappan S Chetty, Leland Mayne, Sissel Lund-Katz, S Walter Englander, Michael C Phillips
Apolipoprotein E (apoE) plays a critical role in cholesterol transport in both peripheral circulation and brain. Human apoE is a polymorphic 299-residue protein in which the less common E4 isoform differs from the major E3 isoform only by a C112R substitution. ApoE4 interacts with lipoprotein particles and with the amyloid-β peptide, and it is associated with increased incidence of cardiovascular and Alzheimer's disease. To understand the structural basis for the differences between apoE3 and E4 functionality, we used hydrogen-deuterium exchange coupled with a fragment separation method and mass spectrometric analysis to compare their secondary structures at near amino acid resolution...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28072416/preclinical-amyloid-pathology-biomarker-positivity-effects-on-tau-pathology-and-neurodegeneration
#12
K Höglund, S Kern, A Zettergren, A Börjesson-Hansson, H Zetterberg, I Skoog, K Blennow
Brain autopsy and biomarker studies indicate that the pathology of Alzheimer's disease (AD) is initiated at least 10-20 years before clinical symptoms. This provides a window of opportunity to initiate preventive treatment. However, this emphasizes the necessity for biomarkers that identify individuals at risk for developing AD later in life. In this cross-sectional study, originating from three epidemiologic studies in Sweden (n=1428), the objective was to examine whether amyloid pathology, as determined by low cerebrospinal fluid (CSF) concentration of the 42 amino acid form of β-amyloid (Aβ42), is associated with biomarker evidence of other pathological changes in cognitively healthy elderly...
January 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28059047/the-elusive-nature-of-apoe-%C3%AE%C2%B54-in-mid-adulthood-understanding-the-cognitive-profile
#13
Claire Lancaster, Naji Tabet, Jennifer Rusted
OBJECTIVES: The apolipoprotein E (APOE) ε4 allele is an established risk factor for dementia, yet this genetic variant is associated with a mixed cognitive profile across the lifespan. This study undertakes both a systematic and meta-analytic review of research investigating APOE-related differences in cognition in mid-adulthood, when detrimental effects of the allele may first be detectable. METHODS: Thirty-six papers investigating the behavioral effects of APOE ε4 in mid-adulthood (defined as a mean sample age between 35 and 60 years) were reviewed...
January 6, 2017: Journal of the International Neuropsychological Society: JINS
https://www.readbyqxmd.com/read/28057414/apoe-apoe-receptors-and-the-synapse-in-alzheimer-s-disease
#14
REVIEW
Courtney Lane-Donovan, Joachim Herz
As the population ages, neurodegenerative diseases such as Alzheimer's disease (AD) are becoming a significant burden on patients, their families, and health-care systems. Neurodegenerative processes may start up to 15 years before outward signs and symptoms of AD, as evidenced by data from AD patients and mouse models. A major genetic risk factor for late-onset AD is the ɛ4 isoform of apolipoprotein E (ApoE4), which is present in almost 20% of the population. In this review we discuss the contribution of ApoE receptor signaling to the function of each component of the tripartite synapse - the axon terminal, the postsynaptic dendritic spine, and the astrocyte - and examine how these systems fail in the context of ApoE4 and AD...
January 2, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28052883/association-of-dietary-cholesterol-and-egg-intakes-with-the-risk-of-incident-dementia-or-alzheimer-disease-the-kuopio-ischaemic-heart-disease-risk-factor-study
#15
Maija Pt Ylilauri, Sari Voutilainen, Eija Lönnroos, Jaakko Mursu, Heli Ek Virtanen, Timo T Koskinen, Jukka T Salonen, Tomi-Pekka Tuomainen, Jyrki K Virtanen
BACKGROUND: There is little information about the associations of intakes of cholesterol and eggs, a major source of dietary cholesterol, with the risk of cognitive decline in general populations or in carriers of apolipoprotein E ɛ4 (APO-E4), a major risk factor for dementia. OBJECTIVE: We investigated the associations of cholesterol and egg intakes with incident dementia, Alzheimer disease (AD), and cognitive performance in middle-aged and older men from Eastern Finland...
January 4, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28035934/the-association-between-plasma-ceramides-and-sphingomyelins-and-risk-of-alzheimer-s-disease-differs-by-sex-and-apoe-in-the-baltimore-longitudinal-study-of-aging
#16
Michelle M Mielke, Norman J Haughey, Dingfen Han, Yang An, Veera Venkata Ratnam Bandaru, Constantine G Lyketsos, Luigi Ferrucci, Susan M Resnick
BACKGROUND: Cellular and animal studies demonstrated relationships between sphingolipid metabolism and Alzheimer's disease (AD) pathology. High blood ceramide levels have been shown to predict cognitive impairment and AD, but these studies had small sample sizes and did not assess differences in risk by sex or APOE genotype. OBJECTIVE: To determine whether plasma ceramides and sphingomyelins were associated with risk of AD, and whether the association varied by sex and APOE genotype...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28035926/pleiotropic-effect-of-human-apoe4-on-cerebral-ceramide-and-saturated-fatty-acid-levels
#17
Sandra den Hoedt, Carola I F Janssen, Guiseppe Astarita, Daniele Piomelli, Frank P J Leijten, Simone M Crivelli, Adrie J M Verhoeven, Helga E de Vries, Jochen Walter, Pilar Martinez-Martinez, Eric J G Sijbrands, Amanda J Kiliaan, Monique T Mulder
BACKGROUND: Apolipoprotein E (ApoE) is known for its role in lipid trafficking and the ɛ4 allele is a risk factor for late onset Alzheimer's disease (AD). Recently, aberrant ceramide and fatty acid (FA) levels have been implicated in AD. OBJECTIVE: To determine the specific effects of human ApoE4 (hE4) on cerebral ceramide and FA content during chow or a high fat/high cholesterol (HFHC) diet. METHODS: Cerebral ceramide and FA profiles were determined by LC-MSMS in 15-month-old female wild-type (WT), ApoE-knockout (E0), and hE4-knockin mice fed chow or a HFHC diet for 3 months...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28035917/apolipoprotein-e4-elicits-lysosomal-cathepsin-d-release-decreased-thioredoxin-1-levels-and-apoptosis
#18
Torbjörn Persson, Francesca Lattanzio, Javier Calvo-Garrido, Roberto Rimondini, Marta Rubio-Rodrigo, Erik Sundström, Silvia Maioli, Anna Sandebring-Matton, Ángel Cedazo-Mínguez
The major genetic risk factor for Alzheimer's disease (AD), apolipoprotein E4 (ApoE4), has been suggested to have detrimental effects on neurons, including direct toxicity via apoptosis. Thioredoxin-1 (Trx1) is an endogenous antioxidant protein important for redox regulation and participates in the regulation of apoptosis through the inhibition of apoptosis signal-regulating kinase-1 (Ask-1). In this study, we have investigated the effects of ApoE on Trx1 in the brain. Our results showed that the protein levels of Trx1 were reduced in the hippocampus of ApoE4 targeted replacement (TR) mice compared to ApoE3 TR mice...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28025282/memory-resilience-to-alzheimer-s-genetic-risk-sex-effects-in-predictor-profiles
#19
Kirstie L McDermott, G Peggy McFall, Shea J Andrews, Kaarin J Anstey, Roger A Dixon
OBJECTIVES: Apolipoprotein E (APOE) ɛ4 and Clusterin (CLU) C alleles are risk factors for Alzheimer's disease (AD) and episodic memory (EM) decline. Memory resilience occurs when genetically at-risk adults perform at high and sustained levels. We investigated whether (a) memory resilience to AD genetic risk is predicted by biological and other risk markers and (b) the prediction profiles vary by sex and AD risk variant. METHOD: Using a longitudinal sample of nondemented adults (n = 642, aged 53-95) we focused on memory resilience (over 9 years) to 2 AD risk variants (APOE, CLU)...
December 26, 2016: Journals of Gerontology. Series B, Psychological Sciences and Social Sciences
https://www.readbyqxmd.com/read/28003161/apolipoprotein-e4-causes-early-olfactory-network-abnormalities-and-short-term-olfactory-memory-impairments
#20
Katherine Y Peng, Paul M Mathews, Efrat Levy, Donald A Wilson
While apolipoprotein (Apo) E4 is linked to increased incidence of Alzheimer's disease (AD), there is growing evidence that it plays a role in functional brain irregularities that are independent of AD pathology. However, ApoE4-driven functional differences within olfactory processing regions have yet to be examined. Utilizing knock-in mice humanized to ApoE4 versus the more common ApoE3, we examined a simple olfactory perceptual memory that relies on the transfer of information from the olfactory bulb (OB) to the piriform cortex (PCX), the primary cortical region involved in higher order olfaction...
February 20, 2017: Neuroscience
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