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Apo E4

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https://www.readbyqxmd.com/read/28350795/fine-mapping-of-the-human-leukocyte-antigen-locus-as-a-risk-factor-for-alzheimer-disease-a-case-control-study
#1
Natasha Z R Steele, Jessie S Carr, Luke W Bonham, Ethan G Geier, Vincent Damotte, Zachary A Miller, Rahul S Desikan, Kevin L Boehme, Shubhabrata Mukherjee, Paul K Crane, John S K Kauwe, Joel H Kramer, Bruce L Miller, Giovanni Coppola, Jill A Hollenbach, Yadong Huang, Jennifer S Yokoyama
BACKGROUND: Alzheimer disease (AD) is a progressive disorder that affects cognitive function. There is increasing support for the role of neuroinflammation and aberrant immune regulation in the pathophysiology of AD. The immunoregulatory human leukocyte antigen (HLA) complex has been linked to susceptibility for a number of neurodegenerative diseases, including AD; however, studies to date have failed to consistently identify a risk HLA haplotype for AD. Contributing to this difficulty are the complex genetic organization of the HLA region, differences in sequencing and allelic imputation methods, and diversity across ethnic populations...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28344553/youthful-processing-speed-in-older-adults-genetic-biological-and-behavioral-predictors-of-cognitive-processing-speed-trajectories-in-aging
#2
Nicholas T Bott, Brianne M Bettcher, Jennifer S Yokoyama, Darvis T Frazier, Matthew Wynn, Anna Karydas, Kristine Yaffe, Joel H Kramer
Objective: To examine the impact of genetic, inflammatory, cardiovascular, lifestyle, and neuroanatomical factors on cognitive processing speed (CPS) change over time in functionally intact older adults. Methods: This observational study conducted over two time points, included 120 community dwelling cognitively normal older adults between the ages of 60 and 80 from the University of California San Francisco Memory and Aging Center. Participants were followed with composite measures of CPS, calculated based on norms for 20-30 year-olds...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28337631/upregulation-of-mineralocorticoid-receptor-in-the-hypothalamus-associated-with-a-high-anxiety-like-level-in-apolipoprotein-e4-transgenic-mice
#3
Fan-Tao Meng, Jun Zhao, Hui Fang, Li-Feng Zhang, Hui-Mei Wu, Ya-Jing Liu
Anxiety symptoms occur in a large portion of Alzheimer's disease (AD) patients. ApolipoproteinE-4 (ApoE ε4 allele), a risk factor for AD, has been recognized as an important contributor to psychiatric disorders. In the present study, we aimed to investigate the corticosterone level in relation to anxiety-like behavior changes in transgenic male mice with different glial fibrillary acidic protein (GFAP)-ApoE isoforms. GFAP-ApoE4 transgenic mice aged 3 months showed higher anxiety-like behavior in open field, light-dark box and elevated plus maze tasks compared with that of age-matched GFAP-ApoE3 mice...
March 24, 2017: Behavior Genetics
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/28329797/social-connectedness-perceived-isolation-and-dementia-does-the-social-environment-moderate-the-relationship-between-genetic-risk-and-cognitive-well-being
#5
Judith L Poey, Jeffrey A Burr, J Scott Roberts
Purpose of the Study: This study examined whether the social environment moderates the relationship between the APOE e4 allele and cognitive functioning. Design and Methods: The Aging, Demographics, and Memory Study (ADAMS) data and multinomial logistic regression models were used to investigate these relationships for a nationally representative sample of U.S. adults aged 70 and older (n = 779). Results: Living alone (relative risk ratio [RRR] = 5...
January 24, 2017: Gerontologist
https://www.readbyqxmd.com/read/28326331/effects-of-apolipoprotein-e-isoforms-in-diabetic-nephropathy-of-chinese-type-2-diabetic-patients
#6
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/28324763/interaction-of-apoe-e4-and-poor-glycemic-control-predicts-white-matter-hyperintensity-growth-from-73-to-76
#7
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/28323826/apoe-related-risk-of-mild-cognitive-impairment-and-dementia-for-prevention-trials-an-analysis-of-four-cohorts
#8
Jing Qian, Frank J Wolters, Alexa Beiser, Mary Haan, M Arfan Ikram, Jason Karlawish, Jessica B Langbaum, John M Neuhaus, Eric M Reiman, J Scott Roberts, Sudha Seshadri, Pierre N Tariot, Beth McCarty Woods, Rebecca A Betensky, Deborah Blacker
BACKGROUND: With the onset of prevention trials for individuals at high risk for Alzheimer disease, there is increasing need for accurate risk prediction to inform study design and enrollment, but available risk estimates are limited. We developed risk estimates for the incidence of mild cognitive impairment (MCI) or dementia among cognitively unimpaired individuals by APOE-e4 dose for the genetic disclosure process of the Alzheimer's Prevention Initiative Generation Study, a prevention trial in cognitively unimpaired APOE-e4/e4 homozygote individuals...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28321820/apolipoprotein-e4-suppresses-neuronal-specific-gene-expression-in-maturing-neuronal-progenitor-cells-exposed-to-hiv
#9
Rebeca Geffin, Ricardo Martinez, Alicia de Las Pozas, Biju Issac, Micheline McCarthy
The apolipoprotein ε4 gene allele and the apolipoprotein E4 protein (ApoE4) are important host susceptibility factors linked to neurocognitive disorders associated with HIV infection or Alzheimer's disease. Our previous studies showed differential effects of the two most common human ApoE genotypes, APOE3/3 and APOE3/4, on gene expression by differentiating human neuroepithelial progenitor cells continuously exposed to HIV. To investigate the effects of ApoE3 versus ApoE4 isoforms specifically on maturing neurons, we adapted a human neuronal progenitor cell line, hNP1, with ApoE genotype APOE3/3...
March 20, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28304301/modeling-the-relationships-among-late-life-body-mass-index-cerebrovascular-disease-and-alzheimer-s-disease-neuropathology-in-an-autopsy-sample-of-1-421-subjects-from-the-national-alzheimer-s-coordinating-center-data-set
#10
Michael L Alosco, Jonathan Duskin, Lilah M Besser, Brett Martin, Christine E Chaisson, John Gunstad, Neil W Kowall, Ann C McKee, Robert A Stern, Yorghos Tripodis
The relationship between late-life body mass index (BMI) and Alzheimer's disease (AD) is poorly understood due to the lack of research in samples with autopsy-confirmed AD neuropathology (ADNP). The role of cerebrovascular disease (CVD) in the interplay between late-life BMI and ADNP is unclear. We conducted a retrospective longitudinal investigation and used joint modeling of linear mixed effects to investigate causal relationships among repeated antemortem BMI measurements, CVD (quantified neuropathologically), and ADNP in an autopsy sample of subjects across the AD clinical continuum...
March 13, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28299413/apolipoprotein-e-the-resilience-gene
#11
Lisa M James, Brian E Engdahl, Apostolos P Georgopoulos
The apolipoprotein E (apoE) gene has been implicated in various conditions, most notably Alzheimer's disease and coronary artery disease. A predisposing role of the apoE4 isoform and a protective role of apoE2 isoform in those diseases have been documented. Here we investigated the role of apoE in resilience to trauma. Three hundred and forty-three US veterans were genotyped for apoE and were assessed for their lifetime trauma exposure (trauma score, T) and severity of posttraumatic stress disorder symptoms (PCL)...
March 15, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28292942/the-apoe-receptors-vldlr-and-apoer2-in-central-nervous-system-function-and-disease
#12
Courtney Lane-Donovan, Joachim Herz
The low-density lipoprotein receptor (LDLR) family has long been studied for its role in cholesterol transport and metabolism; however, the identification of apolipoprotein E4 (ApoE4), an LDLR ligand, as a genetic risk factor for late-onset Alzheimers disease (AD) has focused attention on the role this receptor family plays in the central nervous system (CNS). Surprisingly, it was discovered that two LDLR family members, Apolipoprotein E receptor 2 (Apoer2) and very-low-density lipoprotein receptor (Vldlr), play key roles in brain development and adult synaptic plasticity, primarily by mediating Reelin signaling...
March 14, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28291794/few-serum-proteins-mediate-apoe-s-association-with-dementia
#13
Donald R Royall, Safa Al-Rubaye, Ram Bishnoi, Raymond F Palmer
The latent variable "δ" (for "dementia") appears to be uniquely responsible for the dementing aspects of cognitive impairment. Age, depression, gender and the apolipoprotein E (APOE) e4 allele are independently associated with δ. In this analysis, we explore serum proteins as potential mediators of APOE's specific association with δ in a large, ethnically diverse longitudinal cohort, the Texas Alzheimer's Research and Care Consortium (TARCC). APOE was associated only with C-Reactive Protein (CRP), Adiponectin (APN) and Amphiregulin (AREG), although the latter two's associations did not survive Bonferroni correction for multiple comparisons...
2017: PloS One
https://www.readbyqxmd.com/read/28285306/extremely-low-prevalence-of-amyloid-positron-emission-tomography-positivity-in-parkinson-s-disease-without-dementia
#14
Kyoko Mashima, Daisuke Ito, Masashi Kameyama, Takashi Osada, Hajime Tabuchi, Yoshihiro Nihei, Takahito Yoshizaki, Eri Noguchi, Mariko Tanikawa, Takashi Iizuka, Yugaku Date, Yuji Ogata, Tadaki Nakahara, Yu Iwabuchi, Masahiro Jinzaki, Koji Murakami, Norihiro Suzuki
BACKGROUND: Most cases of dementia with Lewy bodies (DLB) show Alzheimer's disease pathology-like senile plaques and neurofibrillary tangles. Several studies have also revealed a high prevalence of positive amyloid imaging with positron emission tomography (PET) in DLB and moderate prevalence in Parkinson's disease (PD) with dementia. However, it remains unclear in PD without dementia as to when the brain β amyloid (Aβ) burden begins and progresses. Our study aimed to determine the prevalence of Aβ deposition in PD without dementia using amyloid PET...
March 11, 2017: European Neurology
https://www.readbyqxmd.com/read/28276521/a-randomized-trial-and-novel-spr-technique-identifies-altered-lipoprotein-ldl-receptor-binding-as-a-mechanism-underlying-elevated-ldl-cholesterol-in-apoe4s
#15
M V Calabuig-Navarro, K G Jackson, C F Kemp, D S Leake, C M Walden, J A Lovegrove, A M Minihane
At a population level APOE4 carriers (~25% Caucasians) are at higher risk of cardiovascular diseases. The penetrance of genotype is however variable and influenced by dietary fat composition, with the APOE4 allele associated with greater LDL-cholesterol elevation in response to saturated fatty acids (SFA). The etiology of this greater responsiveness is unknown. Here a novel surface plasmon resonance technique (SPR) is developed and used, along with hepatocyte (with the liver being the main organ modulating lipoprotein metabolism and plasma lipid levels) uptake studies to establish the impact of dietary fatty acid composition on, lipoprotein-LDL receptor (LDLR) binding, and hepatocyte uptake, according to APOE genotype status...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28272510/apolipoprotein-e4-and-insulin-resistance-interact-to-impair-cognition-and-alter-the-epigenome-and-metabolome
#16
Lance A Johnson, Eileen Ruth S Torres, Soren Impey, Jan F Stevens, Jacob Raber
Apolipoprotein E4 (E4) and type 2 diabetes are major risk factors for cognitive decline and late onset Alzheimer's disease (AD). E4-associated phenotypes and insulin resistance (IR) share several features and appear to interact in driving cognitive dysfunction. However, shared mechanisms that could explain their overlapping pathophysiology have yet to be found. We hypothesized that, compared to E3 mice, E4 mice would be more susceptible to the harmful cognitive effects of high fat diet (HFD)-induced IR due to apoE isoform-specific differences in brain metabolism...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28269773/impact-of-recruitment-methods-in-subjective-cognitive-decline
#17
Carla Abdelnour, Octavio Rodríguez-Gómez, Montserrat Alegret, Sergi Valero, Sonia Moreno-Grau, Ángela Sanabria, Isabel Hernández, Maitee Rosende-Roca, Liliana Vargas, Ana Mauleón, Domingo Sánchez, Ana Espinosa, Gemma Ortega, Alba Pérez-Cordón, Susana Diego, Anna Gailhajanet, Marina Guitart, Óscar Sotolongo-Grau, Agustín Ruiz, Lluís Tárraga, Mercè Boada
BACKGROUND: Recruitment methods can determine sample characteristics in mild cognitive impairment and Alzheimer's disease dementia, but little is known about its influence in subjective cognitive decline (SCD). OBJECTIVE: To determine the influence of two types of recruitment methods in the characteristics of individuals with SCD. METHODS: We select and compare clinical and neuropsychological features, and frequency of APOE ɛ4 allele of 326 subjects with SCD from two cohorts: Open House Initiative (OHI) versus Memory Unit (MU)...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28269770/psychosocial-risk-and-protective-factors-and-incident-mild-cognitive-impairment-and-dementia-in-community-dwelling-elderly-findings-from-the-singapore-longitudinal-ageing-study
#18
Iris Rawtaer, Qi Gao, Ma Shwe Zin Nyunt, Lei Feng, Mei Sian Chong, Wee Shiong Lim, Tih-Shih Lee, Philip Yap, Keng Bee Yap, Tze Pin Ng
BACKGROUND: Indicators of social isolation or support such as living alone, loneliness, being married, and life satisfaction are possible psychosocial risk and protective factors for dementia. OBJECTIVE: We investigate the associations of these overlapping psychosocial factors with incident MCI-dementia (neurocognitive disorder) in a population cohort. METHODS: Using data from 1601 participants of the Singapore Longitudinal Ageing Study (SLAS) who were free of MCI or dementia at baseline and followed up to 8 years, we estimated hazards ratio (HR) of association of living alone, loneliness, being married, and high life satisfaction with incident MCI-dementia...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28269765/central-review-of-amyloid-related-imaging-abnormalities-in-two-phase-iii-clinical-trials-of-bapineuzumab-in-mild-to-moderate-alzheimer-s-disease-patients
#19
Nzeera Ketter, H Robert Brashear, Jennifer Bogert, Jianing Di, Yves Miaux, Achim Gass, Derk D Purcell, Frederik Barkhof, H Michael Arrighi
BACKGROUND: Amyloid-related imaging abnormalities (ARIA) consist of ARIA-E (with effusion or edema) and ARIA-H (hemosiderin deposits [HDs]). OBJECTIVES: To address accurate ascertainment of ARIA identification, a final magnetic resonance imaging (MRI) reading was performed on patients with mild-to-moderate Alzheimer's disease randomized to bapineuzumab IV or placebo during two Phase III trials (APOE ɛ4 allele carriers or noncarriers). METHODS: Final MRI central review consisted of a systematic sequential locked, adjudicated read in 1,331 APOE ɛ4 noncarriers and 1,121 carriers by independent neuroradiologists...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28255746/prospective-associations-of-exercise-and-depressive-symptoms-in-older-adults-the-role-of-apolipoprotein-e4
#20
Po-Wen Ku, Andrew Steptoe, Li-Jung Chen
PURPOSE: Exercise is associated with reduced risk of depressive symptoms at older ages, while recent work suggests that the apolipoprotein E type 4 allele (APOE-e4) may increase risk. There are no studies of whether APOE-e4 moderates the relationship between exercise and later life depressive symptoms. This study aimed to explore whether the prospective associations between exercise and subsequent depressive symptoms were distinct between APOE-e4 carriers and non-carriers using nationwide data...
March 3, 2017: Quality of Life Research
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