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https://www.readbyqxmd.com/read/28211809/the-methylenetetrahydrofolate-reductase-c677t-polymorphism-and-risk-for-late-onset-alzheimer-s-disease-further-evidence-in-an-italian-multicenter-study
#1
Andrea Stoccoro, Pierpaola Tannorella, Maria Grazia Salluzzo, Raffaele Ferri, Corrado Romano, Benedetta Nacmias, Gabriele Siciliano, Lucia Migliore, Fabio Coppedè
BACKGROUND: A functional polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, namely C677T (rs1801133), results in increased Hcy levels and has been associated with risk of late-onset Alzheimer's disease (LOAD). Many investigators reported association between rs1801133 and LOAD risk in Asian populations and in carriers of the apolipoprotein E (APOE) ɛ4 allele, but recent meta-analyses suggest a contribution also in other populations, including Caucasians and/or northern Africans...
February 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28206976/lipid-and-alzheimer-s-disease-genes-associated-with-healthy-aging-and-longevity-in-healthy-oldest-old
#2
Lauren C Tindale, Stephen Leach, John J Spinelli, Angela R Brooks-Wilson
Several studies have found that long-lived individuals do not appear to carry lower numbers of common disease-associated variants than ordinary people; it has been hypothesized that they may instead carry protective variants. An intriguing type of protective variant is buffering variants that protect against variants that have deleterious effects. We genotyped 18 variants in 15 genes related to longevity or healthy aging that had been previously reported as having a gene-gene interaction or buffering effect...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28199971/association-and-interaction-effects-of-alzheimer-s-disease-associated-genes-and-lifestyle-on-cognitive-aging-in-older-adults-in-a-taiwanese-population
#3
Eugene Lin, Shih-Jen Tsai, Po-Hsiu Kuo, Yu-Li Liu, Albert C Yang, Chung-Feng Kao
Genome-wide association studies and meta-analyses implicated that increased risk of developing Alzheimer's diseases (AD) has been associated with the ABCA7, APOE, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB1, HLA-DRB4, INPP5D, MEF2C, MS4A4A, MS4A4E, MS4A6E, NME8, PICALM, PLD3, PTK2B, RIN3, SLC24A4, SORL1, and ZCWPW1 genes. In this study, we assessed whether single nucleotide polymorphisms (SNPs) within these 27 AD-associatedgenes are linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28193256/unbiased-estimates-of-cerebrospinal-fluid-%C3%AE-amyloid-1-42-cutoffs-in-a-large-memory-clinic-population
#4
Daniela Bertens, Betty M Tijms, Philip Scheltens, Charlotte E Teunissen, Pieter Jelle Visser
BACKGROUND: We sought to define a cutoff for β-amyloid 1-42 in cerebrospinal fluid (CSF), a key marker for Alzheimer's disease (AD), with data-driven Gaussian mixture modeling in a memory clinic population. METHODS: We performed a combined cross-sectional and prospective cohort study. We selected 2462 subjects with subjective cognitive decline, mild cognitive impairment, AD-type dementia, and dementia other than AD from the Amsterdam Dementia Cohort. We defined CSF β-amyloid 1-42 cutoffs by data-driven Gaussian mixture modeling in the total population and in subgroups based on clinical diagnosis, age, and apolipoprotein E (APOE) genotype...
February 14, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28183529/hippocampal-thinning-linked-to-longer-tomm40-poly-t-variant-lengths-in-the-absence-of-the-apoe-%C3%AE%C2%B54-variant
#5
Alison C Burggren, Zanjbeel Mahmood, Theresa M Harrison, Prabha Siddarth, Karen Miller, Gary Small, David A Merrill, Susan Bookheimer
INTRODUCTION: The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with apolipoprotein E (APOE), has received attention more recently as a promising gene in Alzheimer's disease (AD) risk. TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. METHODS: In this study, we examined the effects of TOMM40 using high-resolution magnetic resonance imaging in 65 healthy, older subjects with and without the APOE ε4 AD-risk variant...
February 6, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28183528/transethnic-genome-wide-scan-identifies-novel-alzheimer-s-disease-loci
#6
Gyungah R Jun, Jaeyoon Chung, Jesse Mez, Robert Barber, Gary W Beecham, David A Bennett, Joseph D Buxbaum, Goldie S Byrd, Minerva M Carrasquillo, Paul K Crane, Carlos Cruchaga, Philip De Jager, Nilufer Ertekin-Taner, Denis Evans, M Danielle Fallin, Tatiana M Foroud, Robert P Friedland, Alison M Goate, Neill R Graff-Radford, Hugh Hendrie, Kathleen S Hall, Kara L Hamilton-Nelson, Rivka Inzelberg, M Ilyas Kamboh, John S K Kauwe, Walter A Kukull, Brian W Kunkle, Ryozo Kuwano, Eric B Larson, Mark W Logue, Jennifer J Manly, Eden R Martin, Thomas J Montine, Shubhabrata Mukherjee, Adam Naj, Eric M Reiman, Christiane Reitz, Richard Sherva, Peter H St George-Hyslop, Timothy Thornton, Steven G Younkin, Badri N Vardarajan, Li-San Wang, Jens R Wendlund, Ashley R Winslow, Jonathan Haines, Richard Mayeux, Margaret A Pericak-Vance, Gerard Schellenberg, Kathryn L Lunetta, Lindsay A Farrer
BACKGROUND: Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. METHODS: We conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset...
February 6, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28176662/apoe-%C3%AE%C2%B54-allele-relateted-alterations-in-hippocampal-connectivity-in-early-alzheimer-s-disease-support-memory-performance
#7
Matteo De Marco, Annamaria Vallelunga, Francesca Meneghello, Susheel Varma, Alejandro Frangi, Annalena Venneri
BACKGROUND: Whether the presence of the Apolipoprotein E ε4 allele modulates hippocampal connectivity networks in abnormal ageing has yet to be fully clarified. OBJECTIVE: Allele-dependent differences in this pattern of functional connectivity were investigated in patients with very mild neurodegeneration of the Alzheimer's type, carriers and non-carriers of the ε4 allele. METHOD: A seed-based connectivity approach was used. The two groups were similar in demographics, volumetric measures of brain-structure, and cognitive profiles...
February 6, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28174071/milder-alzheimer-s-disease-pathology-in-heart-failure-and-atrial-fibrillation
#8
Luciano A Sposato, Estefanía Ruíz Vargas, Patricia M Riccio, Jon B Toledo, John Q Trojanowski, Walter A Kukull, Lauren E Cipriano, Antonia Nucera, Shawn N Whitehead, Vladimir Hachinski
INTRODUCTION: Heart failure (HF) and atrial fibrillation (AF) have been associated with a higher risk of Alzheimer's disease (AD). Whether HF and AF are related to AD by enhancing AD neuropathological changes is unknown. METHODS: We applied network analyses and multiple logistic regression models to assess the association between HF and AF with severity of AD neuropathology in patients from the National Alzheimer's Coordinating Center database with primary neuropathological diagnosis of AD...
February 4, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28164773/apolipoprotein-e-mediated-modulation-of-adam10-in-alzheimer-s-disease
#9
Ben Shackleton, Fiona Crawford, Corbin Bachmeier
BACKGROUND: The APOE4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). It has been associated with an accumulation of amyloid-β (Aβ) in the brain, which is produced through the sequential cleavage of the amyloid-β precursor protein (AβPP) by β- and γ-secretases. Alternatively, AβPP is also cleaved by α-secretases such as A Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10). OBJECTIVE: While several studies have investigated the impact of apoE on β- and γ-secretase, interactions between apoE and α-secretases have not been fully examined...
February 2, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28164769/change-in-insr-apba2-and-ide-gene-expressions-in-brains-of-alzheimer%C3%A2-s-disease-patients
#10
Isabela Bazzo Da Costa, Roger Willian De Labio, Lucas Trevizani Rasmussen, Gustavo Arruda Viani, Elizabeth Chen, João Villares, Gustavo Turecki, Marília De Arruda Cardoso Smith, Spencer L M Payão
Alzheimer's disease (AD) is defined as a progressive and irreversible neurodegenerative disorder, the onset of which is mainly characterized by decreased cognition, memory loss, and mental confusion. This study sought to quantify mRNA expression of the APBA2, INSR and IDE genes in brain samples from both patients with AD and controls. We investigated the mRNA expression of the APBA2, INSR and IDE genes in 150 RNA samples from the entorhinal cortex, the auditory cortex, and the hippocampus of individuals with AD and elderly controls using real time PCR...
February 2, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28163090/daily-rhythms-of-cognition-related-factors-are-modified-in-an-experimental-model-of-alzheimer-disease
#11
Lorena Navigatore-Fonzo, Andrea Castro, Verónica Pignataro, Marilina Casais, Marisa Garraza, Ana Cecilia Anzulovich
The accumulation of amyloid-β (Aβ) peptides in the brain of Alzheimer disease patients is associated to cognitive deficit, increased oxidative stress, and alterations in the circadian rhythms. Brain-derived neurotrophic factor (BDNF) and Neurogranin (RC3), play an important role in the synaptic plasticity underlying memory and learning. Previously, we observed BDNF and RC3 expression follow a daily rhythmic pattern in the hippocampus of young rats. The objective of this study was to investigate the effects of an intracerebroventricular (i...
February 2, 2017: Brain Research
https://www.readbyqxmd.com/read/28157104/a-multi-cohort-study-of-apoe-%C3%A9-4-and-amyloid-%C3%AE-effects-on-the-hippocampus-in-alzheimer-s-disease
#12
Wasim Khan, Vincent Giampietro, Tobias Banaschewski, Gareth J Barker, Arun L W Bokde, Christian Büchel, Patricia Conrod, Herta Flor, Vincent Frouin, Hugh Garavan, Penny Gowland, Anreas Heinz, Bernd Ittermann, Hervé Lemaître, Frauke Nees, Tomas Paus, Zdenka Pausova, Marcella Rietschel, Michael N Smolka, Andreas Ströhle, Jeurgen Gallinat, Bruno Vellas, Hilkka Soininen, Iwona Kloszewska, Magda Tsolaki, Patrizia Mecocci, Christian Spenger, Victor L Villemagne, Colin L Masters, J-Sebastian Muehlboeck, Lars Bäckman, Laura Fratiglioni, Grégoria Kalpouzos, Lars-Olof Wahlund, Gunther Schumann, Simon Lovestone, Steven C R Williams, Eric Westman, Andrew Simmons
The apolipoprotein E (APOE) gene has been consistently shown to modulate the risk of Alzheimer's disease (AD). Here, using an AD and normal aging dataset primarily consisting of three AD multi-center studies (n = 1,781), we compared the effect of APOE and amyloid-β (Aβ) on baseline hippocampal volumes in AD patients, mild cognitive impairment (MCI) subjects, and healthy controls. A large sample of healthy adolescents (n = 1,387) was also used to compared hippocampal volumes between APOE groups. Subjects had undergone a magnetic resonance imaging (MRI) scan and APOE genotyping...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28149943/the-apoe-%C3%AE%C2%B54-genotype-modulates-csf-ykl-40-levels-and-their-structural-brain-correlates-in-the-continuum-of-alzheimer-s-disease-but-not-those-of-strem2
#13
Juan Domingo Gispert, Gemma C Monté, Marc Suárez-Calvet, Carles Falcon, Alan Tucholka, Santiago Rojas, Lorena Rami, Raquel Sánchez-Valle, Albert Lladó, Gernot Kleinberger, Christian Haass, José Luis Molinuevo
INTRODUCTION: Among other metabolic functions, the apolipoprotein E (APOE) plays a crucial role in neuroinflammation. We aimed at assessing whether APOE ε4 modulates levels of glial cerebrospinal fluid (CSF) biomarkers and their structural cerebral correlates along the continuum of Alzheimer's disease (AD). METHODS: Brain magnetic resonance imaging (MRI) scans were acquired in 110 participants (49 control; 19 preclinical; 27 mild cognitive impairment [MCI] due to AD; 15 mild AD dementia) and CSF concentrations of YKL-40 and sTREM2 were determined...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28143566/apoe-genotype-differentially-modulates-effects-of-anti-a%C3%AE-passive-immunization-in-app-transgenic-mice
#14
Joanna E Pankiewicz, Jairo Baquero-Buitrago, Sandrine Sanchez, Jennifer Lopez-Contreras, Jungsu Kim, Patrick M Sullivan, David M Holtzman, Martin J Sadowski
BACKGROUND: APOE genotype is the foremost genetic factor modulating β-amyloid (Aβ) deposition and risk of sporadic Alzheimer's disease (AD). Here we investigated how APOE genotype influences response to anti-Aβ immunotherapy. METHODS: APPSW/PS1dE9 (APP) transgenic mice with targeted replacement of the murine Apoe gene for human APOE alleles received 10D5 anti-Aβ or TY11-15 isotype control antibodies between the ages of 12 and 15 months. RESULTS: Anti-Aβ immunization decreased both the load of fibrillar plaques and the load of Aβ immunopositive plaques in mice of all APOE backgrounds...
January 31, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28142142/the-rs1277306-variant-of-the-rest-gene-confers-susceptibility-to-cognitive-aging-in-an-elderly-taiwanese-population
#15
Eugene Lin, Shih-Jen Tsai, Po-Hsiu Kuo, Yu-Li Liu, Albert C Yang, Chung-Feng Kao, Cheng-Hung Yang
BACKGROUND/AIMS: There is growing evidence that the RE1-silencing transcription factor (REST) gene may contribute to cognitive aging and Alzheimer diseases. In this replication study, we reassessed whether single nucleotide polymorphisms (SNPs) within the REST gene are linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. METHODS: A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed...
February 1, 2017: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/28140404/particulate-air-pollutants-apoe-alleles-and-their-contributions-to-cognitive-impairment-in-older-women-and-to-amyloidogenesis-in-experimental-models
#16
M Cacciottolo, X Wang, I Driscoll, N Woodward, A Saffari, J Reyes, M L Serre, W Vizuete, C Sioutas, T E Morgan, M Gatz, H C Chui, S A Shumaker, S M Resnick, M A Espeland, C E Finch, J C Chen
Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer's disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women's Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers...
January 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28137305/peripheral-apoe-isoform-levels-in-cognitively-normal-apoe-%C3%AE%C2%B53-%C3%AE%C2%B54-individuals-are-associated-with-regional-gray-matter-volume-and-cerebral-glucose-metabolism
#17
Henrietta M Nielsen, Kewei Chen, Wendy Lee, Yinghua Chen, Robert J Bauer, Eric Reiman, Richard Caselli, Guojun Bu
BACKGROUND: Carriers of the APOE ε4 allele are at increased risk of developing Alzheimer's disease (AD), and have been shown to have reduced cerebral metabolic rate of glucose (CMRgl) in the same brain areas frequently affected in AD. These individuals also exhibit reduced plasma levels of apolipoprotein E (apoE) attributed to a specific decrease in the apoE4 isoform as determined by quantification of individual apoE isoforms in APOE ε4 heterozygotes. Whether low plasma apoE levels are associated with structural and functional brain measurements and cognitive performance remains to be investigated...
January 30, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28135351/association-between-mentally-stimulating-activities-in-late-life-and-the-outcome-of-incident-mild-cognitive-impairment-with-an-analysis-of-the-apoe-%C3%AE%C2%B54-genotype
#18
Janina Krell-Roesch, Prashanthi Vemuri, Anna Pink, Rosebud O Roberts, Gorazd B Stokin, Michelle M Mielke, Teresa J H Christianson, David S Knopman, Ronald C Petersen, Walter K Kremers, Yonas E Geda
Importance: Cross-sectional associations between engagement in mentally stimulating activities and decreased odds of having mild cognitive impairment (MCI) or Alzheimer disease have been reported. However, little is known about the longitudinal outcome of incident MCI as predicted by late-life (aged ≥70 years) mentally stimulating activities. Objectives: To test the hypothesis of an association between mentally stimulating activities in late life and the risk of incident MCI and to evaluate the influence of the apolipoprotein E (APOE) ε4 genotype...
January 30, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28116548/the-interactive-effects-of-age-and-picalm-rs541458-polymorphism-on-cognitive-performance-brain-structure-and-function-in-non-demented-elderly
#19
Zhen Liu, Xiangwei Dai, Junying Zhang, Xin Li, Yaojing Chen, Chao Ma, Kewei Chen, Dantao Peng, Zhanjun Zhang
The PICALM rs541458 T allele has been recognized as a risk factor for late-onset Alzheimer's disease, and age might modulate the effects that genetic factors have on cognitive functions and brain. Thus, the current study intended to examine whether the effects of rs541458 on cognitive functions, brain structure, and function were modulated by age in non-demented Chinese elderly. We enrolled 638 subjects aged 50 to 82 years and evaluated their cognitive functions through a series of neuropsychological tests...
January 23, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28114437/association-of-docosahexaenoic-acid-supplementation-with-alzheimer-disease-stage-in-apolipoprotein-e-%C3%AE%C2%B54-carriers-a-review
#20
Hussein N Yassine, Meredith N Braskie, Wendy J Mack, Katherine J Castor, Alfred N Fonteh, Lon S Schneider, Michael G Harrington, Helena C Chui
Importance: The apolipoprotein E ε4 (APOE4) allele identifies a unique population that is at significant risk for developing Alzheimer disease (AD). Docosahexaenoic acid (DHA) is an essential ω-3 fatty acid that is critical to the formation of neuronal synapses and membrane fluidity. Observational studies have associated ω-3 intake, including DHA, with a reduced risk for incident AD. In contrast, randomized clinical trials of ω-3 fatty acids have yielded mixed and inconsistent results...
January 17, 2017: JAMA Neurology
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