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https://www.readbyqxmd.com/read/29331531/profiles-of-%C3%AE-amyloid-peptides-and-key-secretases-in-brain-autopsy-samples-differ-with-sex-and-apoe-%C3%AE%C2%B54-status-impact-for-risk-and-progression-of-alzheimer-disease
#1
Jennifer N K Nyarko, Maa O Quartey, Paul R Pennington, Ryan M Heistad, Doris Dea, Judes Poirier, Glen B Baker, Darrell D Mousseau
The APOE ε 4 allele was originally reported to contribute to risk of Alzheimer disease (AD) in women, yet male and female AD patient-derived data are routinely pooled. Histopathological hallmarks of AD include neurofibrillary tangles centered on hyperphosphorylated Tau and plaques composed of the β -amyloid (A β) peptide that is derived by sequential secretase-mediated cleavage of the Amyloid Protein Precursor (APP). We chose to examine profiles of A β (1-40), A β (1-42), and N-truncated (i.e. p3-related) fragments in the plaque-associated fraction of autopsied cortical and corresponding hippocampal samples from donors with a diagnosis of early-onset (EOAD) and late-onset (LOAD) AD...
January 10, 2018: Neuroscience
https://www.readbyqxmd.com/read/29322089/the-wisconsin-registry-for-alzheimer-s-prevention-a-review-of-findings-and-current-directions
#2
REVIEW
Sterling C Johnson, Rebecca L Koscik, Erin M Jonaitis, Lindsay R Clark, Kimberly D Mueller, Sara E Berman, Barbara B Bendlin, Corinne D Engelman, Ozioma C Okonkwo, Kirk J Hogan, Sanjay Asthana, Cynthia M Carlsson, Bruce P Hermann, Mark A Sager
The Wisconsin Registry for Alzheimer's Prevention is a longitudinal observational cohort study enriched with persons with a parental history (PH) of probable Alzheimer's disease (AD) dementia. Since late 2001, Wisconsin Registry for Alzheimer's Prevention has enrolled 1561 people at a mean baseline age of 54 years. Participants return for a second visit 4 years after baseline, and subsequent visits occur every 2 years. Eighty-one percent (1270) of participants remain active in the study at a current mean age of 64 and 9 years of follow-up...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29316447/circulating-metabolites-and-general-cognitive-ability-and-dementia-evidence-from-11-cohort-studies
#3
Sven J van der Lee, Charlotte E Teunissen, René Pool, Martin J Shipley, Alexander Teumer, Vincent Chouraki, Debora Melo van Lent, Juho Tynkkynen, Krista Fischer, Jussi Hernesniemi, Andres Metspalu, Archana Singh-Manoux, Aswin Verhoeven, Gonneke Willemsen, Francien A de Leeuw, Holger Wagner, Jenny van Dongen, Johannes Hertel, Kathrin Budde, Ko Willems van Dijk, Leonie Weinhold, M Arfan Ikram, Maik Pietzner, Markus Perola, Michael Wagner, Nele Friedrich, P E Slagboom, Philip Scheltens, Qiong Yang, Robert E Gertzen, Sarah Egert, Shuo Li, Thomas Hankemeier, Catharine E M van Beijsterveldt, Vasan Ramachandran, Wolfgang Maier, Carel F W Peeters, Hans Jörgen Grabe, Alfredo Ramirez, Sudha Seshadri, Toomas Haller, Mika Kivimäki, Veikko Salomaa, Ayşe Demirkan, Dorret Boomsma, Wiesje M van der Flier, Najaf Amin, Cornelia M van Duijn
INTRODUCTION: Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. METHODS: We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined...
January 6, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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
#4
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/29301387/pharmacogenetics-of-vascular-risk-factors-in-alzheimer-s-disease
#5
REVIEW
Ramón Cacabelos, Arun Meyyazhagan, Juan C Carril, Pablo Cacabelos, Óscar Teijido
Alzheimer's disease (AD) is a polygenic/complex disorder in which genomic, epigenomic, cerebrovascular, metabolic, and environmental factors converge to define a progressive neurodegenerative phenotype. Pharmacogenetics is a major determinant of therapeutic outcome in AD. Different categories of genes are potentially involved in the pharmacogenetic network responsible for drug efficacy and safety, including pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes. However, most drugs exert pleiotropic effects that are promiscuously regulated for different gene products...
January 3, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29298649/an-inflammation-related-nutrient-pattern-is-associated-with-both-brain-and-cognitive-measures-in-a-multiethnic-elderly-population
#6
Yian Gu, Jennifer J Manly, Richard P Mayeux, Adam M Brickman
BACKGROUND: Accumulating evidence suggest that dietary factors are associated with Alzheimer's disease, and brain and cognitive health. It is unclear whether inflammation explains this association. OBJECTIVE: To examine whether an inflammation-related nutrient pattern (INP) was associated with neuroimaging and cognitive measures of brain health. METHOD: The current cross-sectional study included 330 non-demented elderly (mean age 79 years at MRI scan) participants in a multi-ethnic, community-based cohort study who had information on nutritional intakes (estimated from food frequency questionnaire), circulating C-reactive protein and interleukin-6 (measured by ELISA), MRI scans, and cognition...
January 1, 2018: Current Alzheimer Research
https://www.readbyqxmd.com/read/29278888/healthy-versus-entorhinal-cortical-atrophy-identification-in-asymptomatic-apoe4-carriers-at-risk-for-alzheimer-s-disease
#7
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/29278101/bayesian-hidden-markov-models-for-delineating-the-pathology-of-alzheimer-s-disease
#8
Kai Kang, Jingheng Cai, Xinyuan Song, Hongtu Zhu
Alzheimer's disease is a firmly incurable and progressive disease. The pathology of Alzheimer's disease usually evolves from cognitive normal, to mild cognitive impairment, to Alzheimer's disease. The aim of this paper is to develop a Bayesian hidden Markov model to characterize disease pathology, identify hidden states corresponding to the diagnosed stages of cognitive decline, and examine the dynamic changes of potential risk factors associated with the cognitive normal-mild cognitive impairment-Alzheimer's disease transition...
January 1, 2017: Statistical Methods in Medical Research
https://www.readbyqxmd.com/read/29276381/a-new-data-analysis-approach-for-measuring-longitudinal-changes-of-metabolism-in-cognitively-normal-elderly-adults
#9
Sepideh Shokouhi, William R Riddle, Hakmook Kang
Introduction: Previously, we discussed several critical barriers in including [18F] fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging of preclinical Alzheimer's disease (AD) subjects. These factors included the reference region selection and intensity normalization of PET images and the within- and across-subject variability of affected brain regions. In this study, we utilized a novel FDG-PET analysis, the regional FDG time correlation coefficient, rFTC, that can address and resolve these barriers and provide a more sensitive way of monitoring longitudinal changes in metabolism of cognitively normal elderly adults...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/29262361/atomistic-insights-into-structural-differences-between-e3-and-e4-isoforms-of-apolipoprotein-e
#10
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/29259249/comparative-profiling-of-cortical-gene-expression-in-alzheimer-s-disease-patients-and-mouse-models-demonstrates-a-link-between-amyloidosis-and-neuroinflammation
#11
Erika Castillo, Julio Leon, Guianfranco Mazzei, Nona Abolhassani, Naoki Haruyama, Takashi Saito, Takaomi Saido, Masaaki Hokama, Toru Iwaki, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Kunihiko Sakumi, Frank M LaFerla, Yusaku Nakabeppu
Alzheimer's disease (AD) is the most common form of dementia, characterized by accumulation of amyloid β (Aβ) and neurofibrillary tangles. Oxidative stress and inflammation are considered to play an important role in the development and progression of AD. However, the extent to which these events contribute to the Aβ pathologies remains unclear. We performed inter-species comparative gene expression profiling between AD patient brains and the App NL-G-F/NL-G-F and 3xTg-AD-H mouse models. Genes commonly altered in App NL-G-F/NL-G-F and human AD cortices correlated with the inflammatory response or immunological disease...
December 19, 2017: Scientific Reports
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
#12
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/29229897/integrative-analysis-to-identify-common-genetic-markers-of-metabolic-syndrome-dementia-and-diabetes
#13
Weihong Zhang, Linlin Xin, Ying Lu
BACKGROUND Emerging data have established links between systemic metabolic dysfunction, such as diabetes and metabolic syndrome (MetS), with neurocognitive impairment, including dementia. The common gene signature and the associated signaling pathways of MetS, diabetes, and dementia have not been widely studied. MATERIAL AND METHODS We exploited the translational bioinformatics approach to choose the common gene signatures for both dementia and MetS. For this we employed "DisGeNET discovery platform". RESULTS Gene mining analysis revealed that a total of 173 genes (86 genes common to all three diseases) which comprised a proportion of 43% of the total genes associated with dementia...
December 12, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29226870/alzheimer-s-disease-progression-factors-influencing-cognitive-decline
#14
Camilla Ferrari, Gemma Lombardi, Cristina Polito, Giulia Lucidi, Silvia Bagnoli, Irene Piaceri, Benedetta Nacmias, Valentina Berti, Debora Rizzuto, Laura Fratiglioni, Sandro Sorbi
BACKGROUND: Alzheimer's disease (AD) patients present high variability in the rate of cognitive decline. Despite the wide knowledge on factors influencing dementia risk, little is known on what accounts for AD progression. Previous studies on this topic have mainly analyzed each factor separately without taking into account the interaction between genetic and non-genetic factors. OBJECTIVE: The aim of the present study is to evaluate the role of demographic, clinical, therapeutic, and genetic factors and their interaction on cognitive decline among newly diagnosed AD patients...
December 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29222591/dementia-with-lewy-bodies-and-parkinson-s-disease-dementia-current-concepts-and-controversies
#15
REVIEW
Kurt A Jellinger
Dementia with Lewy bodies (DLB) and Parkinson's disease-dementia (PDD), although sharing many clinical, neurochemical and morphological features, according to DSM-5, are two entities of major neurocognitive disorders with Lewy bodies of unknown etiology. Despite considerable clinical overlap, their diagnosis is based on an arbitrary distinction between the time of onset of motor and cognitive symptoms: dementia often preceding parkinsonism in DLB and onset of cognitive impairment after onset of motor symptoms in PDD...
December 8, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29221491/a-phase-iii-randomized-trial-of-gantenerumab-in-prodromal-alzheimer-s-disease
#16
Susanne Ostrowitzki, Robert A Lasser, Ernest Dorflinger, Philip Scheltens, Frederik Barkhof, Tania Nikolcheva, Elizabeth Ashford, Sylvie Retout, Carsten Hofmann, Paul Delmar, Gregory Klein, Mirjana Andjelkovic, Bruno Dubois, Mercè Boada, Kaj Blennow, Luca Santarelli, Paulo Fontoura
BACKGROUND: Gantenerumab is a fully human monoclonal antibody that binds aggregated amyloid-β (Aβ) and removes Aβ plaques by Fc receptor-mediated phagocytosis. In the SCarlet RoAD trial, we assessed the efficacy and safety of gantenerumab in prodromal Alzheimer's disease (AD). METHODS: In this randomized, double-blind, placebo-controlled phase III study, we investigated gantenerumab over 2 years. Patients were randomized to gantenerumab 105 mg or 225 mg or placebo every 4 weeks by subcutaneous injection...
December 8, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29220880/development-of-a-new-biochip-array-for-apoe4-classification-from-plasma-samples-using-immunoassay-based-methods
#17
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/29216449/apoe4-accelerates-early-seeding-of-amyloid-pathology
#18
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/29216448/age-dependent-effects-of-apoe-reduction-using-antisense-oligonucleotides-in-a-model-of-%C3%AE-amyloidosis
#19
Tien-Phat V Huynh, Fan Liao, Caroline M Francis, Grace O Robinson, Javier Remolina Serrano, Hong Jiang, Joseph Roh, Mary Beth Finn, Patrick M Sullivan, Thomas J Esparza, Floy R Stewart, Thomas E Mahan, Jason D Ulrich, Tracy Cole, David M Holtzman
The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer disease. Previous studies suggest that reduction of apoE levels through genetic manipulation can reduce Aβ pathology. However, it is not clear how reduction of apoE levels after birth would affect amyloid deposition. We utilize an antisense oligonucleotide (ASO) to reduce apoE expression in the brains of APP/PS1-21 mice homozygous for the APOE-ε4 or APOE-ε3 allele. ASO treatment starting after birth led to a significant decrease in Aβ pathology when assessed at 4 months...
December 6, 2017: Neuron
https://www.readbyqxmd.com/read/29215310/apolipoprotein-e4-mediates-insulin-resistance-associated-cerebrovascular-dysfunction-and-the-post-prandial-response
#20
Lance A Johnson, Eileen Ruth Torres, Sydney Weber Boutros, Esha Patel, Tunde Akinyeke, Nabil J Alkayed, Jacob Raber
Metabolic dysfunction, commonly a result of diets high in saturated fats and sugar, is associated with impaired cognitive function and an increased risk of age-related cognitive decline (ACD) and Alzheimer's disease (AD). Compared to the E3 isoform of apolipoprotein (apoE), the E4 isoform is a major genetic risk factor for ACD, AD, and for developing cognitive impairments following various environmental challenges, including dietary challenges such as a high-fat diet (HFD). Both insulin resistance (IR) and E4 are associated with metabolic and vascular impairments...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
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