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apoe CNS

Courtney Lane-Donovan, Wen Mai Wong, Murat S Durakoglugil, Catherine R Wasser, Shan Jiang, Xunde Xian, Joachim Herz
UNLABELLED: Alzheimer's disease (AD) is the most common form of dementia in individuals over the age of 65 years. The most prevalent genetic risk factor for AD is the ε4 allele of apolipoprotein E (ApoE4), and novel AD treatments that target ApoE are being considered. One unresolved question in ApoE biology is whether ApoE is necessary for healthy brain function. ApoE knock-out (KO) mice have synaptic loss and cognitive dysfunction; however, these findings are complicated by the fact that ApoE knock-out mice have highly elevated plasma lipid levels, which may independently affect brain function...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Laura Mahoney-Sanchez, Abdel Ali Belaidi, Ashley I Bush, Scott Ayton
Apolipoprotein E (ApoE) plays a crucial role in the homeostatic control of lipids in both the periphery and the central nervous system (CNS). In humans, ApoE exists in three different isoforms: ε2, ε3 and ε4. ApoE ε3 is the most common isoform, while the ε4 isoform confers the greatest genetic risk for Alzheimer's disease (AD). However, the mechanisms underlying how ApoE contributes to the pathogenesis of AD are still debated. ApoE has been shown to impact amyloid β (Aβ) deposition and clearance in the brain...
November 2016: Journal of Molecular Neuroscience: MN
Andrea C Bozoki, Monica Zdanukiewicz, David C Zhu
INTRODUCTION: We evaluated the effect of cerebral amyloid-β (Aβ) deposition in cognitively normal (CN) seniors on regional metabolism of specific brain regions known to be affected by p-tau deposition. METHODS: Fluorodeoxyglucose positron emission tomography (FDG-PET), volumetric magnetic resonance imaging scans, and global amyloid standardized uptake value ratios (SUVr) were obtained for 210 CNs from the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI2). Region of interest (ROI) extraction was used to obtain functional SUVr from six bilateral ROIs: amygdala (AM), entorhinal cortex (EC), hippocampus, lateral orbitofrontal, posterior cingulate (PC), and middle temporal gyrus...
August 27, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Dina Safina, Frederik Schlitt, Ramona Romeo, Thorsten Pflanzner, Claus U Pietrzik, Vasanthy Narayanaswami, Frank Edenhofer, Andreas Faissner
The LDL family of receptors and its member low-density lipoprotein receptor-related protein 1 (LRP1) have classically been associated with a modulation of lipoprotein metabolism. Current studies, however, indicate diverse functions for this receptor in various aspects of cellular activities, including cell proliferation, migration, differentiation, and survival. LRP1 is essential for normal neuronal function in the adult CNS, whereas the role of LRP1 in development remained unclear. Previously, we have observed an upregulation of LewisX (LeX) glycosylated LRP1 in the stem cells of the developing cortex and demonstrated its importance for oligodendrocyte differentiation...
August 2016: Glia
J Scott Miners, Polly Clarke, Seth Love
Clusterin, also known as apoJ, is a lipoprotein abundantly expressed within the CNS. It regulates Aβ fibril formation and toxicity and facilitates amyloid-β (Aβ) transport across the blood-brain barrier. Genome-wide association studies have shown variations in the clusterin gene (CLU) to influence the risk of developing sporadic Alzheimer's disease (AD). To explore whether clusterin modulates the regional deposition of Aβ, we measured levels of soluble (NP40-extracted) and insoluble (guanidine-HCl-extracted) clusterin, Aβ40 and Aβ42 by sandwich ELISA in brain regions with a predilection for amyloid pathology - mid-frontal cortex (MF), cingulate cortex (CC), parahippocampal cortex (PH) - and regions with little or no pathology - thalamus (TH) and white matter (WM)...
June 1, 2016: Brain Pathology
Robert W Mahley
ApoE on high-density lipoproteins is primarily responsible for lipid transport and cholesterol homeostasis in the central nervous system (CNS). Normally produced mostly by astrocytes, apoE is also produced under neuropathologic conditions by neurons. ApoE on high-density lipoproteins is critical in redistributing cholesterol and phospholipids for membrane repair and remodeling. The 3 main structural isoforms differ in their effectiveness. Unlike apoE2 and apoE3, apoE4 has markedly altered CNS metabolism, is associated with Alzheimer disease and other neurodegenerative disorders, and is expressed at lower levels in brain and cerebrospinal fluid...
July 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Xilin Zhang, Jin Hu, Li Zhong, Na Wang, Longyu Yang, Chia-Chen Liu, Huifang Li, Xin Wang, Ying Zhou, Yunwu Zhang, Huaxi Xu, Guojun Bu, Jiangxing Zhuang
Apolipoprotein E (apoE) is a major cholesterol carrier that regulates lipid homeostasis by mediating lipid transport from one tissue or cell type to another. In the central neural system (CNS), apoE is mainly produced by astrocytes, and transports cholesterol to neurons via apoE receptors, which are members of the low-density lipoprotein receptor family. The APOEε4 gene is a strong genetic risk factor for late-onset sporadic Alzheimer's disease (AD), likely through its strong effect on the accumulation of amyloid-β (Aβ) peptide...
September 2016: Neuropharmacology
Sarah A Cooley, Robert H Paul, Christine Fennema-Notestine, Erin E Morgan, Florin Vaida, Qianqian Deng, Jie Ashley Chen, Scott Letendre, Ronald Ellis, David B Clifford, Christina M Marra, Ann C Collier, Benjamin B Gelman, Justin C McArthur, J Allen McCutchan, David M Simpson, Susan Morgello, Igor Grant, Beau M Ances
Previous neuroimaging studies suggest a negative relationship between the apolipoprotein (ApoE) ε4 allele and brain integrity in human immunodeficiency virus (HIV)-infected (HIV+) individuals, although the presence of this relationship across adulthood remains unclear. The purpose of this study is to clarify the discrepancies using a large, diverse group of HIV+ individuals and multiple imaging modalities sensitive to HIV. The association of ApoE ε4 with structural neuroimaging and magnetic resonance spectroscopy (MRS) was examined in 237 HIV+ individuals in the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study...
March 28, 2016: Journal of Neurovirology
Idit Maharshak, Shiran Salomon-Zimri, Ran Antes, Ori Liraz, Yael Nisgav, Tami Livnat, Dov Weinberger, Carol A Colton, Arieh S Solomon, Daniel M Michaelson
Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is associated with neuronal and vascular impairments. The retina, which is as an extension of the central nervous system (CNS), is a particularly suitable model for studying developmental and functional aspects of the neuronal and vascular systems. This study investigates the apoE4-dependent developmental effects on the retinal vasculature and neuronal systems and on the levels of apoE and the vascular endothelial growth factor (VEGF) in the retina...
April 2016: Experimental Eye Research
Yuka Atagi, Chia-Chen Liu, Meghan M Painter, Xiao-Fen Chen, Christophe Verbeeck, Honghua Zheng, Xia Li, Rosa Rademakers, Silvia S Kang, Huaxi Xu, Steven Younkin, Pritam Das, John D Fryer, Guojun Bu
Several heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to risk for a number of neurological disorders including Alzheimer disease (AD), Parkinson disease, and frontotemporal dementia. These discoveries have re-ignited interest in the role of neuroinflammation in the pathogenesis of neurodegenerative diseases. TREM2 is highly expressed in microglia, the resident immune cells of the central nervous system. Along with its adaptor protein, DAP12, TREM2 regulates inflammatory cytokine release and phagocytosis of apoptotic neurons...
October 23, 2015: Journal of Biological Chemistry
Charles C Bailey, Lindsey B DeVaux, Michael Farzan
The triggering receptor expressed on myeloid cells 2 (TREM2) is an Ig-like V-type receptor expressed by populations of myeloid cells in the central nervous system and periphery. Loss-of-function mutations in TREM2 cause a progressive, fatal neurodegenerative disorder called Nasu-Hakola disease. In addition, a TREM2 R47H coding variant was recently identified as a risk factor for late-onset Alzheimer disease. TREM2 binds various polyanionic molecules but no specific protein ligands have been identified. Here we show that TREM2 specifically binds apolipoprotein E, a well established participant in Alzheimer disease...
October 23, 2015: Journal of Biological Chemistry
Zane Jaunmuktane, Simon Mead, Matthew Ellis, Jonathan D F Wadsworth, Andrew J Nicoll, Joanna Kenny, Francesca Launchbury, Jacqueline Linehan, Angela Richard-Loendt, A Sarah Walker, Peter Rudge, John Collinge, Sebastian Brandner
More than two hundred individuals developed Creutzfeldt-Jakob disease (CJD) worldwide as a result of treatment, typically in childhood, with human cadaveric pituitary-derived growth hormone contaminated with prions. Although such treatment ceased in 1985, iatrogenic CJD (iCJD) continues to emerge because of the prolonged incubation periods seen in human prion infections. Unexpectedly, in an autopsy study of eight individuals with iCJD, aged 36-51 years, in four we found moderate to severe grey matter and vascular amyloid-β (Aβ) pathology...
September 10, 2015: Nature
Victor Asensi, Julio Collazos, Eulalia Valle-Garay
Pharmacogenetics refers to the effect of single nucleotide polymorphisms (SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction (HSR) is a cost-effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus (HIV) infection...
August 12, 2015: World Journal of Virology
Li-Li Qiu, Mu-Huo Ji, Hui Zhang, Jiao-Jiao Yang, Xiao-Ru Sun, Hui Tang, Jing Wang, Wen-Xue Liu, Jian-Jun Yang
Microglial activation plays a key role in the development of postoperative cognitive dysfunction (POCD). Nox2, one of the main isoforms of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the central nervous system, is a predominant source of reactive oxygen species (ROS) overproduction in phagocytes including microglia. We therefore hypothesized that Nox2-induced microglial activation is involved in the development of POCD. Sixteen-month-old C57BL/6 mice were subjected to exploratory laparotomy with isoflurane anesthesia to mimic the clinical human abdominal surgery...
January 2016: Brain, Behavior, and Immunity
Mitsuhiro Nakato, Michinori Matsuo, Nozomu Kono, Makoto Arita, Hiroyuki Arai, Jun Ogawa, Noriyuki Kioka, Kazumitsu Ueda
PUFAs, which account for 25-30% of the total fatty acids in the human brain, are important for normal brain development and cognitive function. However, it remains unclear how PUFAs are delivered to neurons and exert their effects. In this study, we demonstrated that n-3 and n-6 PUFAs added to the medium are incorporated into membrane phospholipids of primary glial cells from rat cortices, and then secreted as the fatty acid moiety of phospholipids in apoE-containing lipoproteins (LpEs). Tandem mass spectrometry analysis further showed that LpEs secreted from glial cells contain a variety of metabolites of PUFAs produced in glial cells by elongation and unsaturation...
October 2015: Journal of Lipid Research
Pierre Lavenex, Pamela Banta Lavenex, François Cachat, Mario Gehri, Typhaine Juvet
Seizures associated with fever are a common pediatric problem, affecting about 2-7 % of children between 3 months and 5 years of age. Differentiation of febrile seizures from acute symptomatic seizures secondary to central nervous system infections or seizures associated with fever in children with epilepsy is essential to provide appropriate treatment and follow-up care. Here, we tested the hypothesis that children who exhibit simple febrile seizures during early childhood, but do not develop epileptic seizures later in life, might preferentially carry the ApoE2 allele of the gene coding for the apolipoprotein E...
January 2016: Neurological Sciences
Zhi-Gang Zhang, Yan Li, Cheung Toa Ng, You-Qiang Song
Alzheimer's disease (AD) is a complex age-related neurodegenerative disorder of the central nervous system. Since the first description of AD in 1907, many hypotheses have been established to explain its causes. The inflammation theory is one of them. Pathological and biochemical studies of brains from AD individuals have provided solid evidence of the activation of inflammatory pathways. Furthermore, people with long-term medication of anti-inflammatory drugs have shown a reduced risk to develop the disease...
October 2015: Archivum Immunologiae et Therapiae Experimentalis
Vo Van Giau, Eva Bagyinszky, Seong Soo A An, Sang Yun Kim
Apolipoprotein E (APOE) is a lipid-transport protein abundantly expressed in most neurons in the central nervous system. APOE-dependent alterations of the endocytic pathway can affect different functions. APOE binds to cell-surface receptors to deliver lipids and to the hydrophobic amyloid-β peptide, regulating amyloid-β aggregations and clearances in the brain. Several APOE isoforms with major structural differences were discovered and shown to influence the brain lipid transport, glucose metabolism, neuronal signaling, neuroinflammation, and mitochondrial function...
2015: Neuropsychiatric Disease and Treatment
Daniel Alcolea, Pablo Martínez-Lage, Pascual Sánchez-Juan, Javier Olazarán, Carmen Antúnez, Andrea Izagirre, Mirian Ecay-Torres, Ainara Estanga, Montserrat Clerigué, Maria Concepción Guisasola, Domingo Sánchez Ruiz, Juan Marín Muñoz, Miguel Calero, Rafael Blesa, Jordi Clarimón, María Carmona-Iragui, Estrella Morenas-Rodríguez, Eloy Rodríguez-Rodríguez, José Luis Vázquez Higuera, Juan Fortea, Alberto Lleó
OBJECTIVE: To investigate CSF markers involved in amyloid precursor protein processing, neuronal damage, and neuroinflammation in the preclinical stages of Alzheimer disease (AD) and participants with suspected non-Alzheimer pathology (SNAP). METHODS: We collected CSF from 266 cognitively normal volunteers participating in a cross-sectional multicenter study (the SIGNAL study) to investigate markers involved in amyloid precursor protein processing (Aβ42, sAPPβ, β-secretase activity), neuronal damage (total-tau [t-tau], phospho-tau [p-tau]), and neuroinflammation (YKL-40)...
August 18, 2015: Neurology
Pella C Söderhielm, Jacob Andersen, Lachlan Munro, Anne T Nielsen, Anders S Kristensen
The serotonin transporter (SERT) regulates neurotransmission by the biogenic monoamine neurotransmitter serotonin (5-HT, 5-hydroxytryptamine) in the central nervous system, and drugs inhibiting SERT are widely used for the treatment of a variety of central nervous system diseases. The conformational dynamics of SERT transport function and inhibition is currently poorly understood. We used voltage-clamp fluorometry to study conformational changes in human SERT (hSERT) during 5-HT transport and inhibitor binding...
October 2015: Molecular Pharmacology
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