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https://www.readbyqxmd.com/read/28299413/apolipoprotein-e-the-resilience-gene
#1
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/28298911/autoantibodies-against-the-n-methyl-d-aspartate-receptor-subunit-nr1-untangling-apparent-inconsistencies-for-clinical-practice
#2
REVIEW
Hannelore Ehrenreich
This viewpoint review provides an integrative picture of seemingly contradictory work published on N-methyl-d-aspartate receptor 1 (NMDAR1) autoantibodies (AB). Based on the present state of knowledge, it gives recommendations for the clinical decision process regarding immunosuppressive treatment. Brain antigen-directed AB in general and NMDAR1-AB in particular belong to a preexisting autoimmune repertoire of mammals including humans. Specific autoimmune reactive B cells may get repeatedly (perhaps transiently) boosted by various potential stimulants (e...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28298292/cellular-cholesterol-homeostasis-in-alzheimer-s-disease
#3
Ta Yuan Chang, Yoshio Yamauchi, Mazahir Hasan, Catherine Cy Chang
Alzheimer's disease [AD] is the most common form of dementia in older adults. Currently, there is no cure for AD. The hallmark of AD is the accumulation of extracellular amyloid plaques composed of amyloid beta peptides [Abeta; especially Abeta1-42], and neurofibrillary tangles, composed of hyper-phosphorylated tau, accompanied with chronic neuroinflammation. Abeta are derived from the amyloid precursor protein APP. The oligomeric form of Abeta is probably the most neurotoxic species; its accumulation eventually forms the insoluble and aggregated amyloid plaques...
March 15, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28292942/the-apoe-receptors-vldlr-and-apoer2-in-central-nervous-system-function-and-disease
#4
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/28276521/a-randomized-trial-and-novel-spr-technique-identifies-altered-lipoprotein-ldl-receptor-binding-as-a-mechanism-underlying-elevated-ldl-cholesterol-in-apoe4s
#5
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/28274859/longitudinal-lipid-profile-variations-and-clinical-change-in-alzheimer-s-disease-dementia
#6
Fabricio Ferreira de Oliveira, Elizabeth Suchi Chen, Marilia Cardoso Smith, Paulo Henrique Ferreira Bertolucci
Hypercholesterolemia and statin use have been unevenly associated with clinical change in Alzheimer's disease dementia. In this longitudinal study, 192 consecutive outpatients with late-onset Alzheimer's disease dementia were stratified according to APOE haplotypes, and followed for one year to investigate associations of lipid profile variations and lipophilic statin therapy with changes in cognition, caregiver burden, basic and instrumental functionality. Overall, 102 patients (53.1%) carried APOE4+ haplotypes and 90 (46...
March 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28244566/reversible-states-of-physical-and-or-cognitive-dysfunction-a-9-year-longitudinal-study
#7
C Qualls, D L Waters, B Vellas, D T Villareal, P J Garry, A Gallini, S Andrieu
OBJECTIVES: To determine 1) age-adjusted transition probabilities to worsening physical/cognitive function states, reversal to normal cognition/physical function, or maintenance of normal state; 2) whether these transitions are modulated by sex, BMI, education, hypertension (HTN), health status, or APOE4; 3) whether worsening gait speed preceded cognition change, or vice versa. DESIGN: Analysis of 9-year prospective cohort data from the New Mexico Aging Process Study...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/28241308/apolipoprotein-e2-and-e3-but-not-e4-promote-retinal-pathologic-neovascularization
#8
Tomomi Masuda, Masamitsu Shimazawa, Yuhei Hashimoto, Atsushi Kojima, Shinsuke Nakamura, Shinsuke Suemori, Kiyofumi Mochizuki, Hideaki Kawakami, Kazuhide Kawase, Hideaki Hara
Purpose: To determine the relationship between the different isoforms of apolipoprotein E (ApoE) and retinal neovascularization. Methods: The concentrations of ApoE and VEGF in vitreous humor samples with either a macular hole (MH), or diabetic macular edema (DME), or proliferative diabetic retinopathy (PDR) with or without intravitreal injection of bevacizumab (IVB) were measured by ELISA. The effects of each isoform of ApoE on human retinal microvascular endothelial cells (HRMECs) in culture or on the retina of oxygen-induced retinopathy (OIR) mice were investigated...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28241068/liver-x-receptor-agonist-treatment-significantly-affects-phenotype-and-transcriptome-of-apoe3-and-apoe4-abca1-haplo-deficient-mice
#9
Alexis Y Carter, Florent Letronne, Nicholas F Fitz, Anais Mounier, Cody M Wolfe, Kyong Nyon Nam, Valerie L Reeves, Hafsa Kamboh, Iliya Lefterov, Radosveta Koldamova
ATP-binding cassette transporter A1 (ABCA1) controls cholesterol and phospholipid efflux to lipid-poor apolipoprotein E (APOE) and is transcriptionally controlled by Liver X receptors (LXRs) and Retinoic X Receptors (RXRs). In APP transgenic mice, lack of Abca1 increased Aβ deposition and cognitive deficits. Abca1 haplo-deficiency in mice expressing human APOE isoforms, increased level of Aβ oligomers and worsened memory deficits, preferentially in APOE4 mice. In contrast upregulation of Abca1 by LXR/RXR agonists significantly ameliorated pathological phenotype of those mice...
2017: PloS One
https://www.readbyqxmd.com/read/28225543/cuba-s-aging-and-alzheimer-longitudinal-study
#10
Juan de Jesús Llibre-Rodríguez, Adolfo Valhuerdi-Cepero, Ana M López-Medina, Lisseth Noriega-Fernández, Rutbeskia Porto-Álvarez, Milagros A Guerra-Hernández, Rodolfo I Bosch-Bayard, Tania Zayas-Llerena, Elaine Hernandez-Ulloa, Ana L Rodríguez-Blanco, Enrique Salazar-Pérez, Juan C Llibre-Guerra, Jorge J Llibre-Guerra, Beatriz Marcheco-Teruel
Aging and Alzheimer is a prospective, longitudinal cohort study involving 2944 adults aged ≥65 years from selected areas in Cuba's Havana and Matanzas Provinces. This door-to-door study, which began in 2003, includes periodic assessments of the cohort based on an interview; physical exam; anthropometric measurements; and diagnosis of dementia and its subtypes, other mental disorders, and other chronic non-communicable diseases and their risk factors. Information was gathered on sociodemographic characteristics; disability, dependency and frailty; use of health services; and characteristics of care and caregiver burden...
January 2017: MEDICC Review
https://www.readbyqxmd.com/read/28222108/oxidative-stress-mediated-nf%C3%AE%C2%BAb-phosphorylation-upregulates-p62-sqstm1-and-promotes-retinal-pigmented-epithelial-cell-survival-through-increased-autophagy
#11
Chunjuan Song, Sayak K Mitter, Xiaoping Qi, Eleni Beli, Haripriya V Rao, Jindong Ding, Colin S Ip, Hongmei Gu, Debra Akin, William A Dunn, Catherine Bowes Rickman, Alfred S Lewin, Maria B Grant, Michael E Boulton
p62 is a scaffolding adaptor implicated in the clearance of protein aggregates by autophagy. Reactive oxygen species (ROS) can either stimulate or inhibit NFκB-mediated gene expression influencing cellular fate. We studied the effect of hydrogen peroxide (H2O2)-mediated oxidative stress and NFκB signaling on p62 expression in the retinal pigment epithelium (RPE) and investigated its role in regulation of autophagy and RPE survival against oxidative damage. Cultured human RPE cell line ARPE-19 and primary human adult and fetal RPE cells were exposed to H2O2-induced oxidative stress...
2017: PloS One
https://www.readbyqxmd.com/read/28213052/n-3-fatty-acids-mediterranean-diet-and-cognitive-function-in-normal-aging-a-systematic-review
#12
REVIEW
Maria F Masana, Ai Koyanagi, Josep Maria Haro, Stefanos Tyrovolas
BACKGROUND: Intake of n-3 fatty acids and adherence to the Mediterranean diet (MedDiet) have been shown to slow the progression of age-related cognitive decline, but the results are mixed. We summarized and evaluated the effect of n-3 fatty acids and MedDiet on cognitive outcomes in a cognitively healthy aged population. METHODS: Relevant published studies from January 2000 to May 2015 were identified by searching three electronic databases: Pubmed, Web of Science/MEDLINE, and CINHAL...
February 14, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28212683/evidence-for-benefit-of-statins-to-modify-cognitive-decline-and-risk-in-alzheimer-s-disease
#13
Nophar Geifman, Roberta Diaz Brinton, Richard E Kennedy, Lon S Schneider, Atul J Butte
BACKGROUND: Despite substantial research and development investment in Alzheimer's disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, β-amyloid and AD, and several studies have shown a reduced risk for AD and dementia in populations treated with statins. However, while some clinical trials evaluating statins in general AD populations have been conducted, these resulted in no significant therapeutic benefit. By focusing on subgroups of the AD population, it may be possible to detect endotypes responsive to statin therapy...
February 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28209315/impact-of-apoe-genotypes-variations-on-toxoplasma-patients-with-dementia
#14
Raida S Yahya, Soha I Awad, Hatim A El-Baz, Niveen Saudy, Osama A Abdelsalam, Mohamed S Shehab Al-Din
BACKGROUND: Toxoplasma deprives host neuron cells from cholesterol and leads to its ability to potentiate dementia. ApoE intermediates neuronal transmission of cholesterol, which is a key constituent for axonal development, redesigning occasions that are important for education and synaptic arrangement, development of memory and repair of neuron. The aim of this work is to investigate the effect of ApoE genotypes on dementia associated with neurodegeneration in latent Toxoplasma gondii in elderly population...
February 10, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28173832/gene-environment-interaction-between-lead-and-apolipoprotein-e4-causes-cognitive-behavior-deficits-in-mice
#15
Anna K Engstrom, Jessica M Snyder, Nobuyo Maeda, Zhengui Xia
BACKGROUND: Alzheimer's disease (AD) is characterized by progressive cognitive decline and memory loss. Environmental factors and gene-environment interactions (GXE) may increase AD risk, accelerate cognitive decline, and impair learning and memory. However, there is currently little direct evidence supporting this hypothesis. METHODS: In this study, we assessed for a GXE between lead and ApoE4 on cognitive behavior using transgenic knock-in (KI) mice that express the human Apolipoprotein E4 allele (ApoE4-KI) or Apolipoprotein E3 allele (ApoE3-KI)...
February 7, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28164773/apolipoprotein-e-mediated-modulation-of-adam10-in-alzheimer-s-disease
#16
Ben Shackleton, Fiona Crawford, Corbin Bachmeier
BACKGROUND: The APOE4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). It has been associated with an accumulation of amyloid-β (Aβ) in the brain, which is produced through the sequential cleavage of the amyloid-β precursor protein (AβPP) by β- and γ-secretases. Alternatively, AβPP is also cleaved by α-secretases such as A Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10). OBJECTIVE: While several studies have investigated the impact of apoE on β- and γ-secretase, interactions between apoE and α-secretases have not been fully examined...
February 2, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28160067/tau-aggregation-influences-cognition-and-hippocampal-atrophy-in-the-absence-of-beta-amyloid-a-clinico-imaging-pathological-study-of-primary-age-related-tauopathy-part
#17
Keith A Josephs, Melissa E Murray, Nirubol Tosakulwong, Jennifer L Whitwell, David S Knopman, Mary M Machulda, Stephen D Weigand, Bradley F Boeve, Kejal Kantarci, Leonard Petrucelli, Val J Lowe, Clifford R Jack, Ronald C Petersen, Joseph E Parisi, Dennis W Dickson
We investigate whether there is any association between the Braak neurofibrillary tangle (NFT) stage and clinical and MRI features in definite primary age-related tauopathy (PART). We analysed 52 cases with a Braak NFT tangle stage >0 and ≤IV, and a Thal phase of 0 (no beta-amyloid present). Twenty-nine (56%) were female. Median age at death was 88 years (IQR 82-92 years). Fifteen (29%) were TDP-positive (75% TDP stage I), 16 (31%) had argyrophilic grain disease and three (6%) had alpha-synuclein-positive Lewy bodies...
February 3, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28137305/peripheral-apoe-isoform-levels-in-cognitively-normal-apoe-%C3%AE%C2%B53-%C3%AE%C2%B54-individuals-are-associated-with-regional-gray-matter-volume-and-cerebral-glucose-metabolism
#18
Henrietta M Nielsen, Kewei Chen, Wendy Lee, Yinghua Chen, Robert J Bauer, Eric Reiman, Richard Caselli, Guojun Bu
BACKGROUND: Carriers of the APOE ε4 allele are at increased risk of developing Alzheimer's disease (AD), and have been shown to have reduced cerebral metabolic rate of glucose (CMRgl) in the same brain areas frequently affected in AD. These individuals also exhibit reduced plasma levels of apolipoprotein E (apoE) attributed to a specific decrease in the apoE4 isoform as determined by quantification of individual apoE isoforms in APOE ε4 heterozygotes. Whether low plasma apoE levels are associated with structural and functional brain measurements and cognitive performance remains to be investigated...
January 30, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28114437/association-of-docosahexaenoic-acid-supplementation-with-alzheimer-disease-stage-in-apolipoprotein-e-%C3%AE%C2%B54-carriers-a-review
#19
Hussein N Yassine, Meredith N Braskie, Wendy J Mack, Katherine J Castor, Alfred N Fonteh, Lon S Schneider, Michael G Harrington, Helena C Chui
Importance: The apolipoprotein E ε4 (APOE4) allele identifies a unique population that is at significant risk for developing Alzheimer disease (AD). Docosahexaenoic acid (DHA) is an essential ω-3 fatty acid that is critical to the formation of neuronal synapses and membrane fluidity. Observational studies have associated ω-3 intake, including DHA, with a reduced risk for incident AD. In contrast, randomized clinical trials of ω-3 fatty acids have yielded mixed and inconsistent results...
March 1, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28111074/apoe2-apoe3-and-apoe4-differentially-stimulate-app-transcription-and-a%C3%AE-secretion
#20
Yu-Wen Alvin Huang, Bo Zhou, Marius Wernig, Thomas C Südhof
Human apolipoprotein E (ApoE) apolipoprotein is primarily expressed in three isoforms (ApoE2, ApoE3, and ApoE4) that differ only by two residues. ApoE4 constitutes the most important genetic risk factor for Alzheimer's disease (AD), ApoE3 is neutral, and ApoE2 is protective. How ApoE isoforms influence AD pathogenesis, however, remains unclear. Using ES-cell-derived human neurons, we show that ApoE secreted by glia stimulates neuronal Aβ production with an ApoE4 > ApoE3 > ApoE2 potency rank order. We demonstrate that ApoE binding to ApoE receptors activates dual leucine-zipper kinase (DLK), a MAP-kinase kinase kinase that then activates MKK7 and ERK1/2 MAP kinases...
January 26, 2017: Cell
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