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Alzheimer apoe

Dicson Sheeja Malar, Venkatesan Suryanarayanan, Mani Iyer Prasanth, Sanjeev Kumar Singh, Krishnaswamy Balamurugan, Kasi Pandima Devi
Amyloid beta (Aβ) formation is one of the neuropathological hallmarks of Alzheimer's disease (AD), which induces the generation of reactive oxygen species (ROS), further leading to the alteration of several signalling pathways. In the present study, vitexin has been evaluated for its neuroprotective activity against Aβ25-35 induced toxicity in Neuro-2a cells. Results of cell free studies indicated that vitexin significantly inhibited the aggregation of Aβ25-35 . Studies in Neuro-2a cells revealed that Aβ25-35 significantly affected the cell viability by inducing ROS mediated toxicity and apoptosis...
March 12, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Jessica Tulloch, Lesley Leong, Sunny Chen, C Dirk Keene, Steven P Millard, Andrew Shutes-David, Oscar L Lopez, Julia Kofler, Jeffrey A Kaye, Randy Woltjer, Peter T Nelson, Janna H Neltner, Gregory A Jicha, Douglas Galasko, Eliezer Masliah, James B Leverenz, Chang-En Yu, Debby Tsuang
INTRODUCTION: Inheritance of the ε4 allele of apolipoprotein E (APOE) increases a person's risk of developing both Alzheimer's disease (AD) and Lewy body dementia (LBD), yet the underlying mechanisms behind this risk are incompletely understood. The recent identification of reduced APOE DNA methylation in AD postmortem brains prompted this study to investigate APOE methylation in LBD. METHODS: Genomic DNA from postmortem brain tissues (frontal lobe and cerebellum) of neuropathological pure (np) controls and npAD, LBD + AD, and npLBD subjects were bisulfite pyrosequenced...
March 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Jennifer L Etnier, William B Karper, Jeffrey D Labban, Aaron T Piepmeier, Chia-Hao Shih, William N Dudley, Vincent C Henrich, Laurie Wideman
Background: Alzheimer's disease is a progressive disease that degrades cognitive functioning and ultimately results in death. Currently, there is no cure for Alzheimer's disease and, hence, the identification of preventative strategies is important. Physical activity (PA) is a behavioral intervention that holds promise with respect to delaying the onset of Alzheimer's disease. Purpose: The purpose of this study was to explore the differential cognitive benefits achieved in response to PA as a function of a person's genetic risk for AD...
February 5, 2018: Annals of Behavioral Medicine: a Publication of the Society of Behavioral Medicine
Liv Tybjærg Nordestgaard, Anne Tybjærg-Hansen, Katrine Laura Rasmussen, Børge G Nordestgaard, Ruth Frikke-Schmidt
BACKGROUND: Clusterin, also known as apolipoprotein J (apoJ), is one of the most abundantly expressed apolipoproteins in the brain after apolipoprotein E (apoE). Like the ε4 allele of the apolipoprotein E gene (APOE), the clusterin gene (CLU) is a risk locus for Alzheimer's disease, and may play additional roles in atherosclerosis pathogenesis. We tested whether genetic variation in CLU was associated with either Alzheimer's disease or atherosclerosis-related diseases. METHODS: We studied individual data on 103,987 participants from the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS)...
March 14, 2018: BMC Medicine
Mary H Kosmidis, George S Vlachos, Costas A Anastasiou, Mary Yannakoulia, Efthimios Dardiotis, Georgios Hadjigeorgiou, Paraskevi Sakka, Eva Ntanasi, Nikolaos Scarmeas
INTRODUCTION: Study of the epidemiology of dementia to gain insight into putative predisposing and prophylactic factors is the first step toward establishing effective preventive and therapeutic strategies for this ever-growing public health problem. Relevant data in Greece are scattered and outdated. METHODS: We investigated dementia prevalence as part of a population-representative epidemiological study [Hellenic Longitudinal Investigation of Aging and Diet (HELIAD)] in 2 Greek regions...
March 9, 2018: Alzheimer Disease and Associated Disorders
Katelyn L Arnemann, Franziska Stöber, Sharada Narayan, Gil D Rabinovici, William J Jagust
Metabolic brain networks can provide insight into the network processes underlying progression from healthy aging to Alzheimer's disease. We explore the effect of two Alzheimer's disease risk factors, amyloid-β and ApoE ε4 genotype, on metabolic brain networks in cognitively normal older adults (N = 64, ages 69-89) compared to young adults (N = 17, ages 20-30) and patients with Alzheimer's disease (N = 22, ages 69-89). Subjects underwent MRI and PET imaging of metabolism (FDG) and amyloid-β (PIB). Normal older adults were divided into four subgroups based on amyloid-β and ApoE genotype...
2018: NeuroImage: Clinical
Ornit Chiba-Falek, William K Gottschalk, Michael W Lutz
The TOMM40 poly-T is a polymorphism in intron 6 of the TOMM40 gene, which is adjacent to and in linkage disequilibrium with APOE. Roses et al identified the association between the length of TOMM40 poly-T with the risk and age of onset of late-onset Alzheimer's disease (LOAD). Following the original discovery, additional studies found associations between the TOMM40 poly-T and LOAD-related phenotypes independent of APOE genotypes, while others did not replicate these associations. Furthermore, the identity of the TOMM40 poly-T risk allele has been controversial between different LOAD-related phenotypes...
March 7, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
J W Gause, R J Day, C A Caraway, W W Poon, T T Rohn
Recent studies have supported a role for the proteolytic cleavage of apolipoprotein E4 (APOE4) as a potential mechanism for the enhanced dementia risk associated with Alzheimer's disease. To determine whether APOE4 fragmentation is correlated with AD, ELISA assays were performed with cerebral spinal fluid (CSF) and plasma samples utilizing an antibody that specifically detects a 17 kDa amino-terminal fragment (p17) of APOE (nApoECF antibody). In CSF samples, levels of APOE fragmentation were minimal in both neuropathological normals (NPNs) and AD cases and there were no significant differences between the two cohorts across APOE genotypes...
September 2017: Journal of Neurology and Neurological Disorders
Veronica Tisato, Giovanni Zuliani, Marco Vigliano, Giovanna Longo, Eugenia Franchini, Paola Secchiero, Giorgio Zauli, Elvezia Maria Paraboschi, Ajay Vikram Singh, Maria Luisa Serino, Beatrice Ortolani, Amedeo Zurlo, Cristina Bosi, Antonio Greco, Davide Seripa, Rosanna Asselta, Donato Gemmati
Cognitive impairments of different aetiology share alterations in iron and lipid homeostasis with mutual relationships. Since iron and cholesterol accumulation impact on neurodegenerative disease, the associated gene variants are appealing candidate targets for risk and disease progression assessment. In this light, we explored the role of common single nucleotide polymorphisms (SNPs) in the main iron homeostasis genes and in the main lipoprotein transporter gene (APOE) in a cohort of 765 patients with dementia of different origin: Alzheimer's disease (AD) n = 276; vascular dementia (VaD), n = 255; mild cognitive impairment (MCI), n = 234; and in normal controls (n = 1086)...
2018: PloS One
Doris T Zallen
PurposeApolipoprotein-E (APOE) genetic testing to estimate risk for developing late-onset Alzheimer disease is increasingly being offered without prior genetic counseling or preparation. Consumer interest continues to grow, raising the question of how best to conduct such testing.MethodsTwenty-six semistructured interviews were carried out to study the reactions of individuals who had already learned of their higher risk after APOE testing had been done because of a family history of Alzheimer disease, or from genetic tests done for other health-related or general-interest reasons...
March 8, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Ling Li, Fan Zeng, Yu-Hui Liu, Hui-Yun Li, Shu-Yang Dong, Ze-Yan Peng, Yan-Jiang Wang, Hua-Dong Zhou
Polymorphisms of the cholesterol-24S-hydroxylase (CYP46A1) and apolipoprotein E (APOE) genes are risk factors for Alzheimer's disease (AD). Plasma level of 24S-hydroxcholesterol (24-OHC), the metabolite of cholesterol, is thought to correlate with AD. The present study investigated the correlation between these genetic factors and blood 24-OHC and amyloid-beta (Aβ) levels in AD patients. Association analysis, logistic regression, and linear regression were used to analyze the correlation of CYP46A1 and APOE genotypes with blood 24-OHC and Aβ levels and AD risk...
March 7, 2018: Molecular Neurobiology
Giovanna Scapin, Venkata P Dandey, Zhening Zhang, Winifred Prosise, Alan Hruza, Theresa Kelly, Todd Mayhood, Corey Strickland, Clinton S Potter, Bridget Carragher
The insulin receptor (IR) is a dimeric protein that plays a crucial role in controlling glucose homeostasis, regulating lipid, protein and carbohydrate metabolism, and modulating brain neurotransmitter levels1,2 . IR dysfunction has been associated with many diseases, including diabetes, cancer, and Alzheimer's disease1,2,4 . The primary sequence has been known since the 1980s5 , and is composed of an extracellular portion (ectodomain, ECD), a single transmembrane helix and an intracellular tyrosine kinase domain...
February 28, 2018: Nature
Dasha Fuentes, Nidia Fernández, Yenela García, Teidy García, Ana Ruth Morales, Roberto Menéndez
The knockout mouse model, B6.129P2-Apoetm1Unc is homozygotic for the Apolipoprotein E (ApoE) deletion; thus, it is capable of developing hyperlipidemia and atherosclerosis but ApoE is also a lipid-transport protein abundantly expressed in most neurons in the central nervous system, so these animals could also be models of neurodegenerative diseases. The aim of this study was to determine age-related changes in spontaneous behavior and in learning and memory of Apolipoprotein E knockout mice. Spontaneous behavioral measurements included sleeping pattern, motor coordination and balance by rotarod and open field activity, whereas learning and memory tests included forced alternation in Y-maze, novel object recognition and passive avoidance conditioning...
March 3, 2018: Behavioral Sciences
Ida K Karlsson, Alexander Ploner, Yunzhang Wang, Margaret Gatz, Nancy L Pedersen, Sara Hägg
Background: This study aims to investigate if DNA methylation of the apolipoprotein E (APOE) locus affects the risks of dementia, Alzheimeŕs disease (AD) or cardiovascular disease (CVD). Methods: DNA methylation across the APOE gene has previously been categorized into three distinct regions: a hypermethylated region in the promoter, a hypomethylated region in the first two introns and exons and a hypermethylated region in the 3'exon that also harbours the APOE ε2 and ε4 alleles...
March 2, 2018: International Journal of Epidemiology
Bruno Dubois, Stephane Epelbaum, Francis Nyasse, Hovagim Bakardjian, Geoffroy Gagliardi, Olga Uspenskaya, Marion Houot, Simone Lista, Federica Cacciamani, Marie-Claude Potier, Anne Bertrand, Foudil Lamari, Habib Benali, Jean-François Mangin, Olivier Colliot, Remy Genthon, Marie-Odile Habert, Harald Hampel
BACKGROUND: Improved understanding is needed of risk factors and markers of disease progression in preclinical Alzheimer's disease. We assessed associations between brain β-amyloidosis and various cognitive and neuroimaging parameters with progression of cognitive decline in individuals with preclinical Alzheimer's disease. METHODS: The INSIGHT-preAD is an ongoing single-centre observational study at the Salpêtrière Hospital, Paris, France. Eligible participants were age 70-85 years with subjective memory complaints but unimpaired cognition and memory (Mini-Mental State Examination [MMSE] score ≥27, Clinical Dementia Rating score 0, and Free and Cued Selective Reminding Test [FCSRT] total recall score ≥41)...
February 27, 2018: Lancet Neurology
José V Pardo, Joel T Lee
Alzheimer's disease (AD) progresses insidiously over decades. Therefore, study of preclinical AD is critical to identify early pathophysiological changes as potential targets for prevention or treatment. The brain processes at the preclinical stage remain minimally understood. Aside from age, the E4 allele of APOE flags a group at particularly high risk of late-onset AD (LOAD). Studies of these individuals could provide insights about the ontogenesis of AD offering clues for novel treatment strategies. To this end, cognitively normal, APOE*E4 homozygotes from the Alzheimer's Diseases Neuroimaging Research Initiative database (ADNI-LONI) provided fluorodeoxyglucose and amyloid (florbetapir) PET scans ( n = 8 and 7, respectively; mean age 76 years)...
January 2018: ENeuro
Shahzad Ahmad, Christian Bannister, Sven J van der Lee, Dina Vojinovic, Hieab H H Adams, Alfredo Ramirez, Valentina Escott-Price, Rebecca Sims, Emily Baker, Julie Williams, Peter Holmans, Meike W Vernooij, M Arfan Ikram, Najaf Amin, Cornelia M van Duijn
INTRODUCTION: Exploring the role of Alzheimer's disease (AD) implicated pathways in the predementia phase may provide new insight for preventive and clinical trials targeting disease specific pathways. METHODS: We constructed weighted Genetic risk scores, first based on 20 genome-wide significant AD risk variants and second clustering these variants within pathways. Risk scores were investigated for their association with AD, mild cognitive impairment, and brain magnetic resonance imaging phenotypes including white matter lesions, hippocampal volume, and brain volume...
February 26, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Marci M Horn, Kristen M Kennedy, Karen M Rodrigue
Decline in associative memory abilities is a common cognitive complaint among older adults and is detectable in both normal aging and in prodromal Alzheimer's disease (AD). Subjective memory (SM) complaints may serve as an earlier marker of these mnemonic changes; however, previous research examining the predictive utility of SM to observed memory performance yielded inconsistent results. This inconsistency is likely due to other sources of variance that occur with memory decline such as mood/depression issues, presence of apolipoprotein E (APOE ε4) genotype, or beta-amyloid deposition...
February 2018: Psychology and Aging
Jeong Yeon Hwang, Min Soo Byun, Young Min Choe, Jun Ho Lee, Dahyun Yi, Jae-Won Choi, Su Hwan Hwang, Yu Jin Lee, Dong Young Lee
OBJECTIVES: To clarify the relationships between sleep-wake cycle and cerebral β-amyloid (Aβ) deposition in cognitively normal (CN) older adults, focusing primarily on the moderating effects of the APOE ε4 allele. METHODS: The present study included 133 CN older adults who participated in the Korean Brain Aging Study for Early Diagnosis & Prediction of Alzheimer's Disease cohort. All participants underwent [11 C] Pittsburgh compound B-PET imaging to quantify Aβ deposition in the brain and blood sampling for APOE genotyping...
February 28, 2018: Neurology
Mark W Logue, Matthew S Panizzon, Jeremy A Elman, Nathan A Gillespie, Sean N Hatton, Daniel E Gustavson, Ole A Andreassen, Anders M Dale, Carol E Franz, Michael J Lyons, Michael C Neale, Chandra A Reynolds, Xin Tu, William S Kremen
Early identification of younger, non-demented adults at elevated risk for Alzheimer's disease (AD) is crucial because the pathological process begins decades before dementia onset. Toward that end, we showed that an AD polygenic risk score (PRS) could identify mild cognitive impairment (MCI) in adults who were only in their 50s. Participants were 1176 white, non-Hispanic community-dwelling men of European ancestry in the Vietnam Era Twin Study of Aging (VETSA): 7% with amnestic MCI (aMCI); 4% with non-amnestic MCI (naMCI)...
February 27, 2018: Molecular Psychiatry
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