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Alzheimer apoe

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https://www.readbyqxmd.com/read/28102888/genetic-polymorphisms-in-estrogen-metabolic-pathway-associated-with-risks-of-alzheimer-s-disease-evidence-from-a-southern-chinese-population
#1
Lu Hua Chen, Yan Hui Fan, Patrick Yu Ping Kao, Deborah Tip Yin Ho, Joyce Cheuk Tung Ha, Leung Wing Chu, You-Qiang Song
OBJECTIVES: To investigate whether genetic variations on the estrogen metabolic pathway would be associated with risk of Alzheimer's disease (AD). DESIGN: Cross-sectional study. SETTING: Individuals were recruited at the Memory Clinic, Queen Mary Hospital, Hong Kong. PARTICIPANTS: Chinese individuals with (n = 426) and without (n = 350) AD. MEASUREMENTS: All subjects underwent a standardized cognitive assessment and genotyping of four candidate genes on the estrogen metabolic pathway (estrogen receptor α gene (ESR1), estrogen receptor β gene (ESR2), cytochrome P450 19A1 gene (CYP19A1), cytochrome P450 11A1 gene (CYP11A1))...
January 19, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28099631/associations-of-cerebrovascular-metabolism-genotypes-with-neuropsychiatric-symptoms-and-age-at-onset-of-alzheimer-s-disease-dementia
#2
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
#3
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 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28094792/identification-of-a-nuclear-respiratory-factor-1-recognition-motif-in-the-apolipoprotein-e-variant-apoe4-linked-to-alzheimer-s-disease
#4
Anne Urfer-Buchwalder, Roman Urfer
Alzheimer's disease affects tens of millions of people worldwide and its prevalence continues to rise. It is caused by a combination of a subject's heredity, environment, lifestyle, and medical condition. The most significant genetic risk factor for late onset Alzheimer's disease is a variant of the apolipoprotein E gene, APOE4. Here we show that the single nucleotide polymorphism rs429358 that defines APOE4 is located in a short sequence motif repeated several times within exon 4 of apolipoprotein E, reminiscent of the structure of transcriptional enhancers...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088659/altered-cerebral-insulin-response-in-transgenic-mice-expressing-the-epsilon-4-allele-of-the-human-apolipoprotein-e-gene
#5
Marie-Thérèse Traversy, Milène Vandal, Cyntia Tremblay, Marine Tournissac, Ariane Giguère-Rancourt, A David Bennett, Frédéric Calon
Apolipoprotein E epsilon-4 (APOEε4 or APOE4), an allelic variation of the APOE gene, not only increases the risk of developing the late-onset form of Alzheimer's disease (AD), but also influences the outcome of treatment. Indeed, data from clinical studies show that the beneficial effect of insulin on cognition is blunted in APOE4 carriers. To investigate how APOE impacts insulin response, we assessed the effects of an acute insulin injection in APOE3- and APOE4-targeted replacement mice that respectively express the human APOE3 or APOE4 isoform instead of the endogenous murine ApoE protein...
November 30, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28077724/trem2-promotes-microglial-survival-by-activating-wnt-%C3%AE-catenin-pathway
#6
Honghua Zheng, Lin Jia, Chia-Chen Liu, Zhouyi Rong Li Zhong, Longyu Yang, Xiao-Fen Chen, John D Fryer, Xin Wang, Yun-Wu Zhang, Huaxi Xu, Guojun Bu
: Triggering Receptor Expressed on Myeloid cells 2 (TREM2), expressed on myeloid cells including microglia in the central nervous system (CNS), has recently been identified as a risk factor for Alzheimer's disease (AD). TREM2 transmits intracellular signals through its trans-membrane binding partner DNAX-activating protein 12 (DAP12). Homozygous mutations inactivating TREM2 or DAP12 lead to Nasu-Hakola disease (NHD); however, how AD risk-conferring variants increase AD risk is not clear...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28072416/preclinical-amyloid-pathology-biomarker-positivity-effects-on-tau-pathology-and-neurodegeneration
#7
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/28070483/increased-hippocampal-activation-in-apoe-4-carriers-and-non-carriers-with-amnestic-mild-cognitive-impairment
#8
Tammy T Tran, Caroline L Speck, Aparna Pisupati, Michela Gallagher, Arnold Bakker
Increased fMRI activation in the hippocampus is recognized as a signature characteristic of the amnestic mild cognitive impairment (aMCI) stage of Alzheimer's disease (AD). Previous work has localized this increased activation to the dentate gyrus/CA3 subregion of the hippocampus and showed a correlation with memory impairments in those patients. Increased hippocampal activation has also been reported in carriers of the ApoE-4 allelic variation independently of mild cognitive impairment although these findings were not localized to a hippocampal subregion...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28065845/the-effects-of-ppar%C3%AE-on-the-regulation-of-the-tomm40-apoe-c1-genes-cluster
#9
Shobana Subramanian, William K Gottschalk, So Young Kim, Allen D Roses, Ornit Chiba-Falek
Chromosome 19q13.32 is a gene rich region, and has been implicated in multiple human phenotypes in adulthood including lipids traits, Alzheimer's disease, and longevity. Peroxisome Proliferator Activated Receptor Gamma (PPARγ) is a ligand-activated nuclear transcription factor that plays a role in human complex traits that are also genetically associated with the chromosome 19q13.32 region. Here, we study the effects of PPARγ on the regional expression regulation of the genes clustered within chromosome 19q13...
January 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28061383/increased-blood-brain-barrier-permeability-is-associated-with-dementia-and-diabetes-but-not-amyloid-pathology-or-apoe-genotype
#10
Shorena Janelidze, Joakim Hertze, Katarina Nägga, Karin Nilsson, Christer Nilsson, Malin Wennström, Danielle van Westen, Kaj Blennow, Henrik Zetterberg, Oskar Hansson
Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls...
December 5, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28059796/a-common-variant-in-the-mc1r-gene-p-v92m-is-associated-with-alzheimer-s-disease-risk
#11
Gemma Tell-Marti, Joan Anton Puig-Butille, Miriam Potrony, Estel Plana, Celia Badenas, Anna Antonell, Raquel Sanchez-Valle, José L Molinuevo, Alberto Lleó, Daniel Alcolea, Juan Fortea, Ruben Fernandez-Santiago, Jordi Clarimón, Albert Lladó, Susana Puig
Despite the recent identification of some novel risk genes for Alzheimer's disease (AD), the genetic etiology of late-onset Alzheimer's disease (LOAD) remains largely unknown. The inclusion of these novel risk genes to the risk attributable to the APOE gene accounts for roughly half of the total genetic variance in LOAD. The evidence indicates that undiscovered genetic factors may contribute to AD susceptibility. In the present study, we sequenced the MC1R gene in 525 Spanish LOAD patients and in 160 controls...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28057414/apoe-apoe-receptors-and-the-synapse-in-alzheimer-s-disease
#12
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
#13
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/28052734/motor-timing-intraindividual-variability-in-amnestic-mild-cognitive-impairment-and-cognitively-intact-elders-at-genetic-risk-for-alzheimer-s-disease
#14
Christina D Kay, Michael Seidenberg, Sally Durgerian, Kristy A Nielson, J Carson Smith, John L Woodard, Stephen M Rao
INTRODUCTION: Intraindividual variability (IIV) in motor performance has been shown to predict future cognitive decline. The apolipoprotein E-epsilon 4 (APOE-ε4) allele is also a well-established risk factor for memory decline. Here, we present novel findings examining the influence of the APOE-ε4 allele on the performance of asymptomatic healthy elders in comparison to individuals with amnestic MCI (aMCI) on a fine motor synchronization, paced finger-tapping task (PFTT). METHOD: Two Alzheimer's disease (AD) risk groups, individuals with aMCI (n = 24) and cognitively intact APOE-ε4 carriers (n = 41), and a control group consisting of cognitively intact APOE-ε4 noncarriers (n = 65) completed the Rey Auditory Verbal Learning Test and the PFTT, which requires index finger tapping in synchrony with a visual stimulus (interstimulus interval = 333 ms)...
January 4, 2017: Journal of Clinical and Experimental Neuropsychology
https://www.readbyqxmd.com/read/28042517/rust-on-the-brain-from-microbleeds-and-its-relevance-to-alzheimer-studies-invited-commentary-on-cacciottolo-neurobiology-of-aging-2016
#15
M Cacciottolo, T E Morgan, C E Finch
Cerebral microbleeds (MB) and small vessel disease (SVD) with congophilic arterial angiopathy (CAA) are increasingly recognized as a variable factor in AD cognitive impairments. This commentary on our recent report on sex-ApoE interactions in MBs published this February, briefly explores three aspects of MBs that could not be fully discussed therein: I, A possible gap between the prevalence of MBs as detected by MRI and post mortem analysis; II, The role of hemoglobin-degradation products in amyloid-attributed neurodegenerative changes; and III, Possible assessment of MB by cerebrospinal fluid (CSF) assays for iron-related markers to better screen patient subgroups for AD interventions...
November 2016: Journal of Alzheimer's Disease and Parkinsonism
https://www.readbyqxmd.com/read/28039523/high-sensitivity-cardiac-troponin-i-and-nt-probnp-as-predictors-of-incident-dementia-and-alzheimer-s-disease-the-finrisk-study
#16
Juho Tynkkynen, Jussi A Hernesniemi, Tiina Laatikainen, Aki S Havulinna, Perttu Salo, Stefan Blankenberg, Tanja Zeller, Veikko Salomaa
Cardiac troponin and N-terminal pro-brain natriuretic peptide (NT-proBNP) are known to associate with incident dementia. The purpose of our study was to examine whether high-sensitivity cardiac troponin I (hs-TnI) and NT-proBNP are associated with incident dementia and Alzheimer's disease (AD) independently of each other. Our study was a part of the national population-based health examination survey, FINRISK 1997, with a total sample of 7114 subjects, including 407 incident dementia cases and 319 AD cases during the follow-up time of 18 years...
December 30, 2016: Journal of Neurology
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
#17
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
#18
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
#19
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...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28034305/sorl1-gene-plasma-biomarkers-and-the-risk-of-alzheimer-s-disease-for-the-han-chinese-population-in-taiwan
#20
Cheng-Ta Chou, Yi-Chu Liao, Wei-Ju Lee, Shuu-Jiun Wang, Jong-Ling Fuh
BACKGROUND: The sortilin-related receptor 1 (SORL1) gene, regulating the trafficking and recycling of amyloid precursor protein, has been related to Alzheimer's disease (AD) and mild cognitive impairment (MCI). The aim of the present study was to investigate the relationship between SORL1 polymorphisms, plasma concentrations of amyloid-beta (Aβ) isoforms, and AD and MCI susceptibility for a Han Chinese population in Taiwan. METHODS: Eight single-nucleotide polymorphisms (SNPs) in SORL1 and the apolipoprotein E gene (APOE) ε4 alleles were genotyped in 798 patients with AD, 157 patients with MCI, and 401 control subjects...
December 30, 2016: Alzheimer's Research & Therapy
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