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https://www.readbyqxmd.com/read/29338921/faster-progression-from-mci-to-probable-ad-for-carriers-of-a-single-nucleotide-polymorphism-associated-with-type-2-diabetes
#1
Hugo Girard, Olivier Potvin, Scott Nugent, Caroline Dallaire-Théroux, Stephen Cunnane, Simon Duchesne
Sporadic Alzheimer's disease (AD), as opposed to its autosomal dominant form, is likely caused by a complex interaction of genetic, environmental, and health lifestyle factors. Twin studies indicate that sporadic AD heritability could be between 58% and 79%, around half of which is explained by the ε4 allele of the apolipoprotein E (APOE4). We hypothesized that genes associated with known risk factors for AD, namely hypertension, hypercholesterolemia, obesity, diabetes, and cardiovascular disease, would contribute significantly to the remaining heritability...
December 7, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29334498/evidence-based-interpretation-of-amyloid-%C3%AE-pet-results-a-clinician-s-tool
#2
David Bergeron, Rik Ossenkoppele, Robert Jr Laforce
BACKGROUND: Amyloid-β positron emission tomography (PET) allows for in vivo detection of fibrillar amyloid plaques, a pathologic hallmark of Alzheimer's disease (AD). However, amyloid-β PET interpretation is limited by the imperfect correlation between PET and autopsy, and the fact that it is positive in about 20% to 30% of cognitively normal individuals and non-AD dementias, especially when older or carrying the ε4 allele of apolipoprotein E (ApoE4). When facing a positive amyloid PET, clinicians have to evaluate the probability of a pathologic false positive as well as the probability of amyloid positivity being age-related, comorbid to a primary non-AD dementia (clinicopathologic false positive)...
January 12, 2018: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/29307083/in-thai-nationals-the-apoe4-allele-affects-multiple-domains-of-neuropsychological-biobehavioral-and-social-functioning-thereby-contributing-to-alzheimer-s-disorder-while-the-apoe3-allele-protects-against-neuropsychiatric-symptoms-and-psychosocial-deficits
#3
Sookjaroen Tangwongchai, Thitiporn Supasitthumrong, Solaphat Hemrunroj, Chavit Tunvirachaisakul, Phenphichcha Chuchuen, Natnicha Houngngam, Thiti Snabboon, Ittipol Tawankanjanachot, Yuthachai Likitchareon, Kamman Phanthumchindad, Michael Maes
The apolipoprotein E epsilon 4 (ApoE4) allele is the strongest genetic risk factor for Alzheimer's disorder (AD) and is associated with semantic and episodic memory deficits. The aim of this study was to examine the associations between ApoE alleles (E2, E3, E4) and genotypes and neuropsychological tests, behavioral functions, and dementia symptoms as assessed using Consortium to Establish a Registry for Alzheimer's Disease (CERAD). This study included 60 patients with Alzheimer's disorder (AD), 60 with mild cognitive disorder (MCI), and 62 normal volunteers...
January 6, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29278888/healthy-versus-entorhinal-cortical-atrophy-identification-in-asymptomatic-apoe4-carriers-at-risk-for-alzheimer-s-disease
#4
Kyoko Konishi, Ridha Joober, Judes Poirier, Kathleen MacDonald, Mallar Chakravarty, Raihaan Patel, John Breitner, Véronique D Bohbot
Early detection of Alzheimer's disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ɛ4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ɛ4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments...
December 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29278785/gender-related-increase-of-tropomyosin-1-abundance-in-platelets-of-alzheimer-s-disease-and-mild-cognitive-impairment-patients
#5
Christina Maria Reumiller, Georg Johannes Schmidt, Ina Dhrami, Ellen Umlauf, Eduard Rappold, Maria Zellner
The incidence of Alzheimer's disease (AD) is higher in elderly women than in men. The molecular background for this gender-related risk, however, is largely unknown. In a previous proteomics study we identified significantly elevated levels of monoamine oxidase-B and tropomyosin-1 in AD patients together with significant changes of the genetic AD risk factors apolipoprotein E4 (APOE4) and glutathione S-transferase omega 1 (GSTO1) in platelets - a promising source for AD blood biomarkers. The present study aimed to investigate the gender-specificity as well as disease-stage dependency of these biomarkers in AD patients and those with mild cognitive impairment (MCI)...
December 23, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29262361/atomistic-insights-into-structural-differences-between-e3-and-e4-isoforms-of-apolipoprotein-e
#6
Angana Ray, Navjeet Ahalawat, Jagannath Mondal
Among various isoforms of Apolipoprotein E (ApoE), the E4 isoform (ApoE4) is considered to be the strongest risk factor for Alzheimer's disease, whereas the E3 isoform (ApoE3) is neutral to the disease. Interestingly, the sequence of ApoE4 differs from its wild-type ApoE3 by a single amino acid C112R in the 299-amino-acid-long sequence. Hence, the puzzle remains: how a single-amino-acid difference between the ApoE3 and ApoE4 sequences can give rise to structural dissimilarities between the two isoforms, which can potentially lead to functional differences with significant pathological consequences...
December 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29246571/generation-and-characterization-of-human-induced-pluripotent-stem-cell-hipsc-lines-from-an-alzheimer-s-disease-asui003-a-and-non-demented-control-asui004-a-patient-homozygous-for-the-apolipoprotein-e4-apoe4-risk-variant
#7
Nicholas Brookhouser, Ping Zhang, Richard Caselli, Jean J Kim, David A Brafman
Although the majority of late-onset Alzheimer's disease (AD) patients are labeled sporadic, multiple genetic risk variants have been identified, the most powerful and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene. Here, we generated human induced pluripotent stem cell (hiPSC) lines from the peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient [ASUi003-A] and a non-demented control (NDC) patient [ASUi004-A] homozygous for the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed pluripotency markers, exhibited a normal karyotype, and retained the ability to differentiate into cells representative of the three germ layers...
December 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29220880/development-of-a-new-biochip-array-for-apoe4-classification-from-plasma-samples-using-immunoassay-based-methods
#8
Sigrun Badrnya, Tara Doherty, Ciaran Richardson, Robert I McConnell, John V Lamont, Michael Veitinger, Stephen P FitzGerald, Maria Zellner, Ellen Umlauf
BACKGROUND: Apolipoprotein E (APOE) is a key player in lipid transport and metabolism and exists in three common isoforms: APOE2, APOE3 and APOE4. The presence of the E4 allelic variant is recognized as a major genetic risk factor for dementia and other chronic (neuro)degenerative diseases. The availability of a validated assay for rapid and reliable APOE4 classification is therefore advantageous. METHODS: Biochip array technology (BAT) was successfully applied to identify directly the APOE4 status from plasma within 3 h, through simultaneous immunoassay-based detection of both specific APOE4 and total APOE levels...
December 7, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29216455/seeds-of-destruction-new-mechanistic-insights-into-the-role-of-apolipoprotein-e4-in-alzheimer-s-disease
#9
Robert Vassar
Apolipoprotein E4 (apoE4) is the strongest genetic risk factor for Alzheimer's disease. Despite nearly 25 years of research, the mechanism by which apoE4 confers increased risk for Alzheimer's disease remains enigmatic. In this issue of Neuron, Liu et al. (2017) and Huynh et al. (2017) shed new light on this important question.
December 6, 2017: Neuron
https://www.readbyqxmd.com/read/29216449/apoe4-accelerates-early-seeding-of-amyloid-pathology
#10
Chia-Chen Liu, Na Zhao, Yuan Fu, Na Wang, Cynthia Linares, Chih-Wei Tsai, Guojun Bu
Accumulation and aggregation of amyloid-β (Aβ) in the brain is an initiating step in the pathogenesis of Alzheimer's disease (AD). The ε4 allele of apolipoprotein E (apoE) gene is the strongest genetic risk factor for late-onset AD. Although there is strong evidence showing that apoE4 enhances amyloid pathology, it is not clear what the critical stage(s) is during amyloid development in which apoE4 has the strongest impact. Using apoE inducible mouse models, we show that increased expression of astrocytic apoE4, but not apoE3, during the seeding stage of amyloid development enhanced amyloid deposition and neuritic dystrophy in amyloid model mice...
December 6, 2017: Neuron
https://www.readbyqxmd.com/read/29203090/regional-patterns-of-gray-matter-volume-hypometabolism-and-beta-amyloid-in-groups-at-risk-of-alzheimer-s-disease
#11
Miranka Wirth, Alexandre Bejanin, Renaud La Joie, Eider M Arenaza-Urquijo, Julie Gonneaud, Brigitte Landeau, Audrey Perrotin, Florence Mézenge, Vincent de La Sayette, Béatrice Desgranges, Gaël Chételat
Alzheimer's disease (AD) is characterized by the presence of β-amyloid (Aβ) deposition and neurodegeneration. To seek for signs of such pathologies, we compared regional biomarker degrees and patterns of Aβ deposition, glucose hypometabolism, and gray matter volume (GMV) reduction in 3 groups at risk of AD. In elderly carriers of the apolipoprotein E ε4 (APOE4, n = 17), patients with subjective cognitive decline (n = 16), and patients with mild cognitive impairment (n = 30), head-to-head intermodality comparisons were performed on cross-sectional structural magnetic resonance images as well as 18F-fluorodeoxyglucose and 18F-florbetapir positron emission tomography scans...
November 7, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29182706/clinical-effects-of-tramiprosate-in-apoe4-4-homozygous-patients-with-mild-alzheimer-s-disease-suggest-disease-modification-potential
#12
S Abushakra, A Porsteinsson, P Scheltens, C Sadowsky, B Vellas, J Cummings, S Gauthier, J A Hey, A Power, P Wang, L Shen, M Tolar
BACKGROUND: Alzheimer's Disease (AD) patients homozygous for the APOE4 allele (APOE4/4) have a distinct clinical and biological phenotype with high levels of beta amyloid (Aβ) pathology and toxic Aβ oligomers. Tramiprosate, an oral agent that inhibits Aβ monomer aggregation into toxic oligomers, was evaluated in two Phase 3 Mild to Moderate AD studies which did not show efficacy in the overall population. Re-analyses of these trials showed the most consistent clinical benefits in APOE4/4 patients...
2017: Journal of Prevention of Alzheimer's Disease
https://www.readbyqxmd.com/read/29182703/clinical-effects-of-oral-tramiprosate-in-apoe4-4-homozygous-patients-with-mild-alzheimer-s-disease-suggest-disease-modification
#13
M N Sabbagh
No abstract text is available yet for this article.
2017: Journal of Prevention of Alzheimer's Disease
https://www.readbyqxmd.com/read/29179578/impact-of-ssri-therapy-on-risk-of-conversion-from-mild-cognitive-impairment-to-alzheimer-s-dementia-in-individuals-with-previous-depression
#14
Claudia Bartels, Michael Wagner, Steffen Wolfsgruber, Hannelore Ehrenreich, Anja Schneider
OBJECTIVE: Depression is associated with an increased risk of Alzheimer's disease. Research has shown that the selective serotonin reuptake inhibitor (SSRI) citalopram decreases amyloid-β generation and plaque load. The authors evaluated the impact of SSRI treatment on CSF biomarkers and progression from mild cognitive impairment (MCI) to Alzheimer's dementia. METHOD: Data sets from 755 currently nondepressed participants from the longitudinal Alzheimer's Disease Neuroimaging Initiative were evaluated by Kaplan-Meier analysis and analyses of variance and covariance with ApoE4 status and age as covariates...
November 28, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/29174637/apolipoprotein-e4-exacerbates-ethanol-induced-neurotoxicity-through-augmentation-of-oxidative-stress-and-apoptosis-in-n2a-app-cells
#15
Jie Li, Jian Cheng
Neuronal loss is a prominent phenomenon in Alzheimer's disease (AD) and alcohol-induced brain damage. Alcohol abuse is associated with an increased risk of AD, regardless of the type of alcoholic beverage. Furthermore, the detrimental effect of excessive alcohol consumption on the risk of AD is exacerbated among people carrying apolipoprotein E (APOE) ε4 allele, the major genetic risk factor for AD. However, how APOE ε4 and alcohol abuse synergistically enhance the possibility of AD is unclear. Here we show that in N2a cells stably expressing human APP695 (N2a-APP), high-concentration ethanol-induced neurotoxicity was significantly augmented in the presence of apoE4 protein, compared with apoE3 protein...
November 21, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29172001/co-expression-of-glia-maturation-factor-and-apolipoprotein-e4-in-alzheimer-s-disease-brain
#16
Ramasamy Thangavel, Sachin M Bhagavan, Swathi Beladakere Ramaswamy, Spurthi Surpur, Raghav Govindarajan, Duraisamy Kempuraj, Smita Zaheer, Sudhanshu Raikwar, Mohammad E Ahmed, Govindhasamy Pushpavathi Selvakumar, Shankar S Iyer, Asgar Zaheer
Apolipoprotein E4 (ApoE4) is a major genetic risk factor for Alzheimer's disease (AD). The E4 allele of ApoE plays a crucial role in the inflammatory and neurodegenerative processes associated with AD. This is evident from the multiple effects of the ApoE isoforms in amyloid-β (Aβ) aggregation. Glia maturation factor (GMF) is a brain-specific neuroinflammatory protein that we have previously demonstrated to be significantly upregulated in various regions of AD brains compared to non-AD control brains and that it induces neurodegeneration...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29169581/vitamin-d-status-is-associated-with-executive-function-a-decade-later-data-from-the-women-s-healthy-ageing-project
#17
Alicia M Goodwill, Stephen Campbell, Steven Simpson, Maria Bisignano, Cherie Chiang, Lorraine Dennerstein, Cassandra Szoeke
OBJECTIVES: Vitamin D deficiency has been associated with cognitive decline and dementia in older adults. However, there is a paucity of studies assessing whether this association manifests from midlife. Given the long prodromal stage of dementia, we investigated the association between midlife vitamin D and cognition 10 years later. STUDY DESIGN: 252 participants (aged 55-67 years) from the Women's Healthy Ageing Project had baseline (2002) vitamin D and neuropsychological measures assessed...
January 2018: Maturitas
https://www.readbyqxmd.com/read/29169407/the-clinical-significance-of-plasma-clusterin-and-a%C3%AE-in-the-longitudinal-follow-up-of-patients-with-alzheimer-s-disease
#18
Jung-Lung Hsu, Wei-Ju Lee, Yi-Chu Liao, Shuu-Jiun Wang, Jong-Ling Fuh
BACKGROUND: Clusterin and beta-amyloid (Aβ) are involved in the pathogenesis of Alzheimer's disease (AD). The clinical significance of plasma clusterin and Aβ in AD progression remains controversial. METHODS: We recruited 322 patients with AD and 88 controls between August 2012 and June 2013. All participants were evaluated at baseline with a clinical assessment, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) scales. Patients with AD were evaluated annually with the MMSE and Neuropsychiatric Inventory (NPI) scale during the 2-year follow-up period...
November 23, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29163138/perspective-insights-into-disease-progression-diagnostics-and-therapeutic-approaches-in-alzheimer-s-disease-a-judicious-update
#19
REVIEW
Arif Tasleem Jan, Mudsser Azam, Safikur Rahman, Angham M S Almigeiti, Duk Hwan Choi, Eun Ju Lee, Qazi Mohd Rizwanul Haq, Inho Choi
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive accumulation of β-amyloid fibrils and abnormal tau proteins in and outside of neurons. Representing a common form of dementia, aggravation of AD with age increases the morbidity rate among the elderly. Although, mutations in the ApoE4 act as potent risk factors for sporadic AD, familial AD arises through malfunctioning of APP, PSEN-1, and-2 genes. AD progresses through accumulation of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) in brain, which interfere with neuronal communication...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29159264/the-effects-of-apolipoprotein-e-genotype-%C3%AE-synuclein-deficiency-and-sex-on-brain-synaptic-and-alzheimer-s-disease-related-pathology
#20
Roni Bar, Anat Boehm-Cagan, Ishai Luz, Yarden Kleper-Wall, Daniel M Michaelson
Introduction: Alzheimer's disease (AD) and synucleinopathies share common pathological mechanisms. Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for AD, also increases the risk for dementia in pure synucleinopathies. We presently examined the effects of α-synuclein deficiency (α-syn-/-) and sex on apoE4-driven pathologies. Methods: AD-related, synaptic, and vascular markers were analyzed in female and male α-syn-/- and α-syn+/+ apoE4, apoE3, and apoE3/E4 mice...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
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