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ApoE myelin

Andrew R Hoy, Martina Ly, Cynthia M Carlsson, Ozioma C Okonkwo, Henrik Zetterberg, Kaj Blennow, Mark A Sager, Sanjay Asthana, Sterling C Johnson, Andrew L Alexander, Barbara B Bendlin
Brain changes associated with Alzheimer's disease (AD) begin decades before disease diagnosis. While β-amyloid plaques and neurofibrillary tangles are defining features of AD, neuronal loss and synaptic pathology are closely related to the cognitive dysfunction. Brain imaging methods that are tuned to assess degeneration of myelinated nerve fibers in the brain (collectively called white matter) include diffusion tensor imaging (DTI) and related techniques, and are expected to shed light on disease-related loss of structural connectivity...
2017: PloS One
Jo Mailleux, Tim Vanmierlo, Jeroen Fj Bogie, Elien Wouters, Dieter Lütjohann, Jerome Ja Hendriks, Jack van Horssen
OBJECTIVE: We sought to determine the liver X receptor (LXR) ligands present in human macrophages after myelin phagocytosis and whether LXRs are activated in multiple sclerosis (MS) lesions. METHODS: We used real-time quantitative polymerase chain reaction (PCR) and immunohistochemistry to determine expression of LXRs and their response genes in human phagocytes after myelin phagocytosis and in active MS lesions. We used gas chromatographic/mass spectrometric analysis to determine LXR-activating oxysterols and cholesterol precursors present and formed in myelin and myelin-incubated cells, respectively...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
Matti Myllykoski, Petri Kursula
The 2H phosphoesterase family contains enzymes with two His-X-Ser/Thr motifs in the active site. 2H enzymes are found in all kingdoms of life, sharing little sequence identity despite the conserved overall fold and active site. For many 2H enzymes, the physiological function is unknown. Here, we studied the structure of the 2H family member LigT from Escherichia coli both in the apo form and complexed with different active-site ligands, including ATP, 2'-AMP, 3'-AMP, phosphate, and NADP+. Comparisons to the well-characterized vertebrate myelin enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) highlight specific features of the catalytic cycle and substrate recognition in both enzymes...
2017: PloS One
Radouil Tzekov, Clint Dawson, Megan Orlando, Benoit Mouzon, Jon Reed, James Evans, Gogce Crynen, Michael Mullan, Fiona Crawford
Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue was examined for cellularity, myelin content, protein and lipid changes...
2016: PloS One
Zhen Gu, Fengqiao Li, Yi Ping Zhang, Lisa B E Shields, Xiaoling Hu, Yiyan Zheng, Panpan Yu, Yongjie Zhang, Jun Cai, Michael P Vitek, Christopher B Shields
OBJECTIVE: Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimetic peptide COG112 has previously demonstrated therapeutic efficacy on functional and histological recovery in a mouse experimental autoimmune encephalomyelitis (EAE) model of human MS. In the current study, we further investigated whether COG112 promotes remyelination and improves functional recovery in lysolecithin induced focal demyelination in the white matter of spinal cord in mice...
April 2013: Journal of Neurology & Neurophysiology
Sooyeon Lee, Stephanie Amici, Hagai Tavori, Waylon M Zeng, Steven Freeland, Sergio Fazio, Lucia Notterpek
Haploinsufficiency of peripheral myelin protein 22 (PMP22) causes hereditary neuropathy with liability to pressure palsies, a peripheral nerve lesion induced by minimal trauma or compression. As PMP22 is localized to cholesterol-enriched membrane domains that are closely linked with the underlying actin network, we asked whether the myelin instability associated with PMP22 deficiency could be mediated by involvement of the protein in actin-dependent cellular functions and/or lipid raft integrity. In peripheral nerves and cells from mice with PMP22 deletion, we assessed the organization of filamentous actin (F-actin), and actin-dependent cellular functions...
November 26, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
J A Opara, E Małecka, J Szczygiel
Traumatic brain injury is a leading cause of death and disability worldwide. Every year, about 1.5 million affected people die and several millions receive emergency treatment. Most of the burden (90%) is in low and middle-income countries. The costs of care depend on the level of disability. The burden of care after traumatic brain injury is caused by disability as well as by psychosocial and emotional sequelae of injury. The final consequence of brain injury is the reduction of quality of life. It is very difficult to predict the outcome after traumatic brain injury...
June 15, 2014: Journal of Medicine and Life
Denise D Correa, Jaya Satagopan, Raymond E Baser, Kenneth Cheung, Elizabeth Richards, Michael Lin, Sasan Karimi, John Lyo, Lisa M DeAngelis, Irene Orlow
OBJECTIVE: The goal of this study was to assess whether the APOE ε4 allele and other APOE single nucleotide polymorphisms (SNPs) influence neuropsychological and neuroimaging outcomes in patients with brain tumors. METHODS: Two hundred eleven patients with brain tumors participated in the study. All patients completed standardized neuropsychological tests and provided a blood sample for APOE genotyping. Ratings of white matter abnormalities were performed on MRI scans...
July 22, 2014: Neurology
Okko T Pyykkö, Miikka Lumela, Jaana Rummukainen, Ossi Nerg, Toni T Seppälä, Sanna-Kaisa Herukka, Anne M Koivisto, Irina Alafuzoff, Lakshman Puli, Sakari Savolainen, Hilkka Soininen, Juha E Jääskeläinen, Mikko Hiltunen, Henrik Zetterberg, Ville Leinonen
BACKGROUND: The significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) is unknown. OBJECTIVE: To investigate the role of soluble APP (sAPP) and amyloid beta (Aβ) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy Aβ and hyperphosphorylated tau (HPτ) findings. METHODS: The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available...
2014: PloS One
Walter Maetzler, Anja Apel, Markus Langkamp, Christian Deuschle, Sarah Selina Dilger, Johannes Georg Stirnkorb, Claudia Schulte, Erwin Schleicher, Thomas Gasser, Daniela Berg
Naturally occurring autoantibodies (NAbs) against a number of potentially disease-associated cellular proteins, including Amyloid-beta1-42 (Abeta1-42), Alpha-synuclein (Asyn), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and S100 calcium binding protein B (S100B) have been suggested to be associated with neurodegenerative disorders, in particular Alzheimer's (AD) and Parkinson's disease (PD). Whereas the (reduced) occurrence of specific NAbs in AD is widely accepted, previous literature examining the relation of these NAb titres between PD patients and controls, as well as comparing these levels with demographic and clinical parameters in PD patients have produced inconsistent findings...
2014: PloS One
Valerio Leoni, Claudio Caccia
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an abnormal expansion of a CAG repeat in the huntingtin gene. Neurodegeneration of striatum and cortex with a severe atrophy at MRI are common findings in HD. The expression of genes involved in the cholesterol biosynthetic pathway such as HMG-CoA reductase and the levels of cholesterol, lanosterol, lathosterol and 24S-hydroxycholesterol are reduced in the brain, striatum and cortex in several HD mouse models. Mutant huntingtin affects the maturation and translocation of SREBP and cannot up-regulate LXR...
April 11, 2014: Biochemical and Biophysical Research Communications
Jessica M Foley, David H Salat, Nikki H Stricker, Tyler A Zink, Laura J Grande, Regina E McGlinchey, William P Milberg, Elizabeth C Leritz
Possession of the apolipoprotein E4 (APOE4) allele and diabetes risk are independently related to reduced white matter (WM) integrity that may contribute to the development of Alzheimer's disease (AD). The purpose of this study is to examine the interactive effects of APOE4 and diabetes risk on later myelinating WM regions among healthy elderly individuals at risk of AD. A sample of 107 healthy elderly (80 APOE4-/27 APOE4+) individuals underwent structural magnetic resonance imaging/diffusion tensor imaging (DTI)...
May 2014: American Journal of Alzheimer's Disease and Other Dementias
Douglas C Dean, Beth A Jerskey, Kewei Chen, Hillary Protas, Pradeep Thiyyagura, Auttawat Roontiva, Jonathan O'Muircheartaigh, Holly Dirks, Nicole Waskiewicz, Katie Lehman, Ashley L Siniard, Mari N Turk, Xue Hua, Sarah K Madsen, Paul M Thompson, Adam S Fleisher, Matthew J Huentelman, Sean C L Deoni, Eric M Reiman
IMPORTANCE: Converging evidence suggests brain structure alterations may precede overt cognitive impairment in Alzheimer disease by several decades. Early detection of these alterations holds inherent value for the development and evaluation of preventive treatment therapies. OBJECTIVE: To compare magnetic resonance imaging measurements of white matter myelin water fraction (MWF) and gray matter volume (GMV) in healthy infant carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele, the major susceptibility gene for late-onset AD...
January 2014: JAMA Neurology
Saloua Akoudad, Marius de Groot, Peter J Koudstaal, Aad van der Lugt, Wiro J Niessen, Albert Hofman, M Arfan Ikram, Meike W Vernooij
OBJECTIVE: To investigate whether the presence of cerebral microbleeds, which present as focal lesions on imaging, is associated with a diffuse loss of white matter microstructural integrity in the brain. METHODS: In the prospective, population-based Rotterdam Scan Study, a total of 4,493 participants underwent brain MRI to determine microbleed status. With diffusion tensor imaging, global fractional anisotropy (FA) and mean diffusivity (MD) were measured in normal-appearing white matter...
November 26, 2013: Neurology
Timothy M Hughes, Lewis H Kuller, Emma J M Barinas-Mitchell, Rachel H Mackey, Eric M McDade, William E Klunk, Howard J Aizenstein, Ann D Cohen, Beth E Snitz, Chester A Mathis, Steven T Dekosky, Oscar L Lopez
OBJECTIVE: To determine arterial stiffness and β-amyloid (Aβ) deposition in the brain of dementia-free older adults. METHODS: We studied a cohort of 91 dementia-free participants aged 83-96 years. In 2009, participants completed brain MRI and PET imaging using Pittsburgh compound B (PiB; a marker of amyloid plaques in human brain). In 2011, we measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed (e...
November 5, 2013: Neurology
Vishnu Priyanka Reddy Chichili, Yucheng Xiao, J Seetharaman, Theodore R Cummins, J Sivaraman
The neuronal-voltage gated sodium channel (VGSC), Na(V)1.6, plays an important role in propagating action potentials along myelinated axons. Calmodulin (CaM) is known to modulate the inactivation kinetics of Na(V)1.6 by interacting with its IQ motif. Here we report the crystal structure of apo-CaM:Na(V)1.6IQ motif, along with functional studies. The IQ motif of Na(V)1.6 adopts an α-helical conformation in its interaction with the C-lobe of CaM. CaM uses different residues to interact with Na(V)1.6IQ motif depending on the presence or absence of Ca²⁺...
2013: Scientific Reports
Hee Jin Kim, Byoung Seok Ye, Cindy W Yoon, Hanna Cho, Young Noh, Geon Ha Kim, Yae Seul Choi, Jung-Hyun Kim, Seun Jeon, Jong Min Lee, Jae Seung Kim, Yearn Seong Choe, Kyung Han Lee, Sung Tae Kim, Changsoo Kim, Dae Ryong Kang, Chang-Seok Ki, Jae Hong Lee, David J Werring, Michael W Weiner, Duk L Na, Sang Won Seo
The relationship between the apolipoprotein E ε4 allele (APOE4) and factors associated with vascular cognitive impairment (VCI) is unclear. We aimed to examine the effects of APOE4 on brain amyloid beta using Pittsburg compound B (PiB) and subcortical cerebrovascular disease, as assessed by lacunes and white matter hyperintensities (WMH) in subcortical VCI (SVCI) patients. We recruited 230 subjects with normal cognition, 111 subjects with cognitive impairment due to clinically defined Alzheimer's disease (ADCI), and 134 subjects with clinically defined SVCI...
November 2013: Neurobiology of Aging
Shawn M Newlander, Alan Chu, Usha S Sinha, Po H Lu, George Bartzokis
PURPOSE: To identify regional differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) using customized preprocessing before voxel-based analysis (VBA) in 14 normal subjects with the specific genes that decrease (apolipoprotein [APO] E ε2) and that increase (APOE ε4) the risk of Alzheimer's disease. MATERIALS AND METHODS: Diffusion tensor images (DTI) acquired at 1.5 Tesla were denoised with a total variation tensor regularization algorithm before affine and nonlinear registration to generate a common reference frame for the image volumes of all subjects...
February 2014: Journal of Magnetic Resonance Imaging: JMRI
R Scott Mackin, Philip Insel, Duygu Tosun, Susanne G Mueller, Norbert Schuff, Diana Truran-Sacrey, Sky T Raptentsetsang, Jun-Young Lee, Clifford R Jack, Paul S Aisen, Ronald C Petersen, Michael W Weiner
OBJECTIVE: To assess the effect of subsyndromal symptoms of depression (SSD) on ratings of disability for individuals with mild cognitive impairment (MCI). METHODS: Data from 405 MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were analyzed. Participants were evaluated at baseline and at 6-month intervals over 2 years. Severity of depressive symptoms was rated utilizing the Geriatric Depression Scale. Disability was assessed utilizing the Functional Assessment Questionnaire (FAQ)...
September 2013: American Journal of Geriatric Psychiatry
Lauren E Salminen, Peter R Schofield, Elizabeth M Lane, Jodi M Heaps, Kerrie D Pierce, Ryan Cabeen, David H Laidlaw, Erbil Akbudak, Thomas E Conturo, Stephen Correia, Robert H Paul
The epsilon 4 (e4) isoform of apolipoprotein E (ApoE) is a known genetic risk factor for suboptimal brain health. Morphometry studies of brains with Alzheimer's disease have reported significant alterations in temporal lobe brain structure of e4 carriers, yet it remains unclear if the presence of an e4 allele is associated with alterations in the microstructure of white matter fiber bundles in healthy populations. The present study used quantitative tractography based on diffusion tensor imaging (qtDTI) to examine the influence of the e4 allele on temporal lobe fiber bundle lengths (FBLs) in 64 healthy older adults with at least one e4 allele (carriers, N = 23) versus no e4 allele (non-carriers, N = 41)...
September 2013: Brain Imaging and Behavior
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