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Apo E4

Moeko Noguchi-Shinohara, Chiemi Abe, Sohshi Yuki-Nozaki, Chiaki Dohmoto, Ayaka Mori, Koji Hayashi, Syutaro Shibata, Yoshihisa Ikeda, Kenji Sakai, Kazuo Iwasa, Masami Yokogawa, Mai Ishimiya, Hiroyuki Nakamura, Hidehiro Yokoji, Kiyonobu Komai, Hiroyuki Nakamura, Masahito Yamada
BACKGROUND: Antioxidants like vitamins C and E may minimize the risk for Alzheimer's disease. OBJECTIVE: We examined whether vitamins C and E modify the apolipoprotein E (APOE) E4-related risks for developing cognitive decline. METHODS: We conducted a population-based prospective study including Japanese residents aged 65 years from Nakajima, Japan. The participants received an evaluation of cognitive function and underwent blood tests including tests for vitamins C and E levels and APOE phenotypes...
May 11, 2018: Journal of Alzheimer's Disease: JAD
Blanca Romero-Moraleda, Rocío Cupeiro Coto, Domingo González-Lamuño, Teresa Amigo, Barbara Szendrei, Miguel Ángel Rojo-Tirado, Francisco Javier Calderón, Ana Belén Peinado
BACKGROUND: apolipoprotein E (ApoE) polymorphism is a genetic determinant of lipid and lipoprotein levels and the risk for coronary heart disease. OBJECTIVE: to evaluate the impact of ApoE2allele in lipid plasma levels and the influence of a healthy hypocaloric diet plus a controlled physical activity on the lipid profile, we performed a study in a cohort of overweight and obese healthy subjects (Body Mass Index (BMI) between 25 and 34.9 kg·m-2). METHODS: one hundred eighty participants (96 women), aged 18-50 years participated in a 22 weeks weight loss intervention based on same dietary treatment and different controlled exercise programs...
March 1, 2018: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
Michael Peitz, Tamara Bechler, Catrin Cornelia Thiele, Monika Veltel, Melanie Bloschies, Klaus Fliessbach, Alfredo Ramirez, Oliver Brüstle
Alzheimer's disease (AD) is most the frequent neurodegenerative disease, and the APOE ε4 allele is the most prominent risk factor for late-onset AD. Here, we present an iPSC line generated from peripheral blood cells of a male AD patient employing Sendai virus vectors encoding the transcription factors OCT4, SOX2, KLF4 and c-MYC. The characterized iPSC line expresses typical human pluripotency markers and shows differentiation into all three germ layers, complete reprogramming vector clearance, a normal SNP genotype and maintenance of the APOE ε4/ε4 allele...
April 23, 2018: Stem Cell Research
Jun-Hee Lee, Sang-Min Hong, Yun-A Shin
The apolipoprotein E ( APOE ) gene has been suggested to be associated with stroke and dementia. However, the effects of exercise training on dementia according to the APOE genotype are not consistent to those reported by previous studies. Therefore, we examined the effects of exercise training on stroke risk factors including blood pressure, lipid profiles, homocysteine (Hcy) concentrations, and cognitive function according to the APOE genotype in stroke patients. We examined the stroke risk factors, Hcy, and cognitive function in 28 ischemic stroke patients before and after 6 months of exercise training...
April 2018: Journal of Exercise Rehabilitation
Christine Kimbacher, Christian Paar, Andrea Freystetter, Joerg Berg
BACKGROUND: Genotyping for clinically important single nucleotide polymorphisms (SNPs) is performed by many clinical routine laboratories. To support testing, quality controls and reference materials are needed. Those may be derived from residual patient samples, left over samples of external quality assurance schemes, plasmid DNA or DNA from cell lines. DNAs from cell lines are commutable and available in large amounts. METHODS: DNA from 38 cell lines were examined for suitability as controls in 11 SNP assays that are frequently used in a clinical routine laboratory: FV (1691G>A), FII (20210G>A), PAI-1 4G/5G polymorphism, MTHFR (677C>T, 1298A>C), HFE (H63D, S65C, C282Y), APOE (E2, E3, E4), LPH (-13910C>T), UGT1A1 (*28, *36, *37), TPMT (*2, *3A, *3B, *3C), VKORC1 (-1639G>A, 1173C>T), CYP2C9 (*2, *3, *5)...
May 1, 2018: Clinical Laboratory
Israa M Shatwan, Kristian Hillert Winther, Basma Ellahi, Peter Elwood, Yoav Ben-Shlomo, Ian Givens, Margaret P Rayman, Julie A Lovegrove, Karani S Vimaleswaran
BACKGROUND: Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors...
April 30, 2018: Lipids in Health and Disease
Gerwyn Morris, Michael Berk, Michael Maes, Basant K Puri
The classical amyloid cascade model for Alzheimer's disease (AD) has been challenged by several findings. Here, an alternative molecular neurobiological model is proposed. It is shown that the presence of the APOE ε4 allele, altered miRNA expression and epigenetic dysregulation in the promoter region and exon 1 of TREM2, as well as ANK1 hypermethylation and altered levels of histone post-translational methylation leading to increased transcription of TNFA, could variously explain increased levels of peripheral and central inflammation found in AD...
April 29, 2018: Molecular Neurobiology
Julius S Ngwa, Thomas V Fungwe, Oyonumo Ntekim, Joanne S Allard, Sheree M Johnson, Chimene Castor, Lennox Graham, Sheeba Nadarajah, Richard F Gillum, Thomas O Obisesan
BACKGROUND: It is increasingly evident that high blood pressure can promote reduction in global and regional brain volumes. While these effects may preferentially affect the hippocampus, reports are inconsistent. METHODS: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we examined the relationships of hippocampal volume to pulse pressure (PPR) and systolic (SBP) and diastolic (DBP) blood pressure according to apolipoprotein (APOE) ɛ4 positivity and cognitive status...
April 25, 2018: Dementia and Geriatric Cognitive Disorders
Maddalena Macedoni, Tinka Hovnik, Emil Plesnik, Primoz Kotnik, Natasa Bratina, Tadej Battelino, Urh Groselj
BACKGROUND AND AIMS: Limited data is available on the factors influencing the lipid profiles and the prevalence of dyslipidemia in children, adolescents and young adults with type 1 diabetes. We aimed at assessing the influences of metabolic control and ApoE genotypes on lipid profiles and the prevalence of dyslipidemia in children, adolescents and young adults with type 1 diabetes. METHODS: Children, adolescents and young adults with type 1 diabetes from our nationwide cohort attending the annual check-up were prospectively included...
April 12, 2018: Atherosclerosis
Brett S East, Gloria Fleming, Kathy Peng, Jonas K Olofsson, Efrat Levy, Paul M Mathews, Donald A Wilson
Apolipoprotein E (ApoE) is an important lipid carrier in both the periphery and the brain. The ApoE ε4 allele (ApoE4) is the single most important genetic risk-factor for Alzheimer's disease (AD) while the ε 2 allele (ApoE2) is associated with a lower risk of AD-related neurodegeneration compared to the most common variant, ε 3 (ApoE3). ApoE genotype affects a variety of neural circuits; however, the olfactory system appears to provide early biomarkers of ApoE genotype effects. Here, we directly compared olfactory behavior and olfactory system physiology across all three ApoE genotypes in 6-month- and 12-month-old mice with targeted replacement for the human ApoE2, ApoE3, or ApoE4 genes...
April 17, 2018: Neuroscience
Shruti Mishra, Tyler M Blazey, David M Holtzman, Carlos Cruchaga, Yi Su, John C Morris, Tammie L S Benzinger, Brian A Gordon
While prior work reliably demonstrates that the APOE ɛ4 allele has deleterious group level effects on Alzheimer disease pathology, the homogeneity of its influence across the lifespan and spatially in the brain remains unknown. Further it is unclear what combinations of factors at an individual level lead to observed group level effects of APOE genotype. To evaluate the impact of the APOE genotype on disease trajectories, we examined longitudinal MRI and PET imaging in a cohort of 497 cognitively normal middle and older aged participants...
April 17, 2018: Brain: a Journal of Neurology
Timothy A Couttas, Nupur Kain, Collin Tran, Zac Chatterton, John B Kwok, Anthony S Don
The greatest risk factor for developing Alzheimer's disease (AD) is aging. The major genetic risk factor for AD is the ɛ4 allele of the APOE gene, encoding the brain's major lipid transport protein, apolipoprotein E (ApoE). The research community is yet to decipher why the ApoE4 variant pre-disposes to AD, and how aging causes the disease. Studies have shown deregulated levels of sphingolipids, including decreased levels of the neuroprotective signaling lipid sphingosine 1-phosphate (S1P), and increased ceramide content, in brain tissue and serum of people with pre-clinical or very early AD...
2018: Journal of Alzheimer's Disease: JAD
Binbin Wang, Suying Bao, Zhigang Zhang, Xueya Zhou, Jing Wang, Yanhui Fan, Yan Zhang, Yan Li, Luhua Chen, Yizhen Jia, Jiang Li, Miaoxin Li, Wenhua Zheng, Nan Mu, Liqiu Wang, Zhe Yu, Dana S M Wong, Yalun Zhang, Joseph Kwan, Henry Ka-Fung Mak, Amirthagowri Ambalavanan, Sirui Zhou, Wangwei Cai, Jin Zheng, Shishu Huang, Guy A Rouleau, Wanling Yang, Ekaterina Rogaeva, Xu Ma, Peter St George-Hyslop, Leung Wing Chu, You-Qiang Song
Alzheimer's disease (AD) is the most common neurodegenerative disorders in the elderly. To identify rare genetic factors other than apolipoprotein E ɛ4 allele (ApoE ɛ4) contributing to the pathogenesis of late-onset AD (LOAD), we conducted a whole-exome analysis of 246 ApoE ɛ4-negative LOAD cases and 172 matched controls in Hong Kong Chinese population. LOAD patients showed a significantly higher burden of rare loss-of-function variants in genes related to immune function than healthy controls. Among the genes involved in immune function, we identified a rare stop-gain variant (p...
March 10, 2018: Neurobiology of Aging
Bevan S Main, Sonia Villapol, Stephanie S Sloley, David J Barton, Maia Parsadanian, Chinyere Agbaegbu, Kathryn Stefos, Mondona S McCann, Patricia M Washington, Olga C Rodriguez, Mark P Burns
BACKGROUND: Traumatic Brain Injury (TBI) is a major cause of disability and mortality, to which there is currently no comprehensive treatment. Blood Brain Barrier (BBB) dysfunction is well documented in human TBI patients, yet the molecular mechanisms that underlie this neurovascular unit (NVU) pathology remains unclear. The apolipoprotein-E (apoE) protein has been implicated in controlling BBB integrity in an isoform dependent manner, via suppression of Cyclophilin A (CypA)-Matrix metallopeptidase-9 (MMP-9) signaling cascades, however the contribution of this pathway in TBI-induced BBB permeability is not fully investigated...
April 4, 2018: Molecular Neurodegeneration
Janina Krell-Roesch, Nathanael T Feder, Rosebud O Roberts, Michelle M Mielke, Teresa J Christianson, David S Knopman, Ronald C Petersen, Yonas E Geda
We conducted a prospective cohort study derived from the population-based Mayo Clinic Study of Aging. We investigated if leisure-time physical activity among individuals with mild cognitive impairment (MCI) was associated with a decreased risk of developing dementia. 280 persons aged≥70 years (median 81 years, 165 males) with MCI and available data from neurologic evaluation, neuropsychological testing, and questionnaire-based physical activity assessment, were followed for a median of 3 years to the outcomes of incident dementia or censoring variables...
March 29, 2018: Journal of Alzheimer's Disease: JAD
David R Borchelt
Inheritance of the E4 allele of the apolipoprotein E gene (APOE4) substantially increases the risk of developing late-onset Alzheimer disease (AD). A large body of evidence has firmly established a role for apoE in modulating the risk of developing the amyloid plaque pathology that is pathognomonic for AD. In this issue of the JCI, Liao and colleagues discovered that antibodies against a nonlipidated form of apoE4 are highly effective in delaying the deposition of amyloid β (Aβ) peptides in mouse models of AD pathology...
May 1, 2018: Journal of Clinical Investigation
Fan Liao, Aimin Li, Monica Xiong, Nga Bien-Ly, Hong Jiang, Yin Zhang, Mary Beth Finn, Rosa Hoyle, Jennifer Keyser, Katheryn B Lefton, Grace O Robinson, Javier Remolina Serrano, Adam P Silverman, Jing L Guo, Jennifer Getz, Kirk Henne, Cheryl Eg Leyns, Gilbert Gallardo, Jason D Ulrich, Patrick M Sullivan, Eli Paul Lerner, Eloise Hudry, Zachary K Sweeney, Mark S Dennis, Bradley T Hyman, Ryan J Watts, David M Holtzman
The apolipoprotein E E4 allele of the APOE gene is the strongest genetic factor for late-onset Alzheimer disease (LOAD). There is compelling evidence that apoE influences Alzheimer disease (AD) in large part by affecting amyloid β (Aβ) aggregation and clearance; however, the molecular mechanism underlying these findings remains largely unknown. Herein, we tested whether anti-human apoE antibodies can decrease Aβ pathology in mice producing both human Aβ and apoE4, and investigated the mechanism underlying these effects...
March 30, 2018: Journal of Clinical Investigation
Fiona C Baker, Negin Sattari, Massimiliano de Zambotti, Aimee Goldstone, William A Alaynick, Sara C Mednick
Age and sex are two of the three major risk factors for Alzheimer's disease (ApoE-e4 allele is the third), with women having a two-fold greater risk for Alzheimer's disease after the age of 75 years. Sex differences have been shown across a wide range of cognitive skills in young and older adults, and evidence supports a role for sex steroids, especially estradiol, in protecting against the development of cognitive decline in women. Sleep may also be a protective factor against age-related cognitive decline, since specific electrophysiological sleep events (e...
March 21, 2018: Neurobiology of Learning and Memory
Zhen Liu, Xiangwei Dai, Wuhai Tao, Huilan Liu, He Li, Caishui Yang, Junying Zhang, Xin Li, Yaojing Chen, Chao Ma, Jing Pei, Haohao Mao, Kewei Chen, Zhanjun Zhang
Exploring how risk genes cumulatively impair brain function in preclinical phase (i.e., in cognitively normal elderly) could provide critical insights into the pathophysiology of Alzheimer's disease (AD). Working memory impairment has always been a considerable cognitive deficit in AD, which is likely under complex genetic control. Though, the APOE ɛ4 allele could damage the working memory performance in normal elderly, dissociable results have been reported. This allele may exert specific effects in contexts with other genetic variants...
March 24, 2018: Human Brain Mapping
Madeleine L Werhane, Kelsey R Thomas, Emily C Edmonds, Katherine J Bangen, My Tran, Alexandra L Clark, Daniel A Nation, Paul E Gilbert, Mark W Bondi, Lisa Delano-Wood
BACKGROUND/OBJECTIVE: The APOE ɛ4 allele and increased vascular risk have both been independently linked to cognitive impairment and dementia. Since few studies have characterized how these risk factors affect everyday functioning, we investigated the relationship between APOE ɛ4 genotype and elevated pulse pressure (PP) on functional change in cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS: 738 normally aging participants underwent APOE genotyping, and baseline PP was calculated from blood pressure indices...
March 16, 2018: Journal of Alzheimer's Disease: JAD
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