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https://www.readbyqxmd.com/read/28808293/targeting-apolipoprotein-e-amyloid-%C3%AE-binding-by-peptoid-cpo_a%C3%AE-17-21%C3%A2-p-ameliorates-alzheimer-s-disease-related-pathology-and-cognitive-decline
#1
Shan Liu, Shinae Park, Grant Allington, Frances Prelli, Yanjie Sun, Mitchell Martá-Ariza, Henrieta Scholtzova, Goutam Biswas, Bernard Brown, Philip B Verghese, Pankaj D Mehta, Yong-Uk Kwon, Thomas Wisniewski
Inheritance of the apolipoprotein E4 (apoE4) genotype has been identified as the major genetic risk factor for late onset Alzheimer's disease (AD). Studies have shown that apoE, apoE4 in particular, binds to amyloid-β (Aβ) peptides at residues 12-28 of Aβ and this binding modulates Aβ accumulation and disease progression. We have previously shown in several AD transgenic mice lines that blocking the apoE/Aβ interaction with Aβ12-28 P reduced Aβ and tau-related pathology, leading to cognitive improvements in treated AD mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800331/alzheimer-s-disease-biomarkers-interactively-influence-physical-activity-mobility-and-cognition-associations-in%C3%A2-a%C3%A2-non-demented-aging-population
#2
Sherilyn Thibeau, G Peggy McFall, Richard Camicioli, Roger A Dixon
BACKGROUND: Alzheimer's disease (AD) risk-reduction strategies (e.g., increasing physical activity, improving mobility) have garnered increasing attention in the literature. However, the effect of such modifiable factors on the preclinical trajectories of brain and cognitive health may be moderated by non-modifiable biomarkers associated with AD. OBJECTIVE: In a longitudinal sample of non-demented older adults, we examine the independent predictors everyday physical activity (EPA) and mobility on executive function (EF) performance and change...
August 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28798312/the-hypothesis-that-helicobacter-pylori-predisposes-to-alzheimer-s-disease-is-biologically-plausible
#3
Contaldi Felice, Capuano Federico, Fulgione Andrea, Aiese Cigliano Riccardo, Sanseverino Walter, Iannelli Domenico, Medaglia Chiara, Capparelli Rosanna
There is epidemiological evidence that H. pylori might predispose to Alzheimer's disease. To understand the cellular processes potentially linking such unrelated events, we incubated the human gastric cells MNK-28 with the H. pylori peptide Hp(2-20). We then monitored the activated genes by global gene expression. The peptide modulated 77 genes, of which 65 are listed in the AlzBase database and include the hallmarks of Alzheimer's disease: APP, APOE, PSEN1, and PSEN2. A large fraction of modulated genes (30 out of 77) belong to the inflammation pathway...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794245/apoe-genotype-and-early-%C3%AE-amyloid-accumulation-in-older-adults-without-dementia
#4
Yen Ying Lim, Elizabeth C Mormino
OBJECTIVE: To clarify associations between APOE ε4 allele and age on longitudinal rates of β-amyloid (Aβ) accumulation within Aβ+ and Aβ- older individuals without dementia. METHODS: We analyzed 595 older adults without dementia classified cross-sectionally as Aβ- (n = 325) and Aβ+ (n = 270) using longitudinal florbetapir PET. The influence of age and APOE genotype on longitudinal accumulation of Aβ was examined with linear mixed models. RESULTS: APOE ε4 and older age were associated with higher risk of being classified as Aβ+ at baseline...
August 9, 2017: Neurology
https://www.readbyqxmd.com/read/28789839/contribution-to-alzheimer-s-disease-risk-of-rare-variants-in-trem2-sorl1-and-abca7-in-1779-cases-and-1273-controls
#5
Céline Bellenguez, Camille Charbonnier, Benjamin Grenier-Boley, Olivier Quenez, Kilan Le Guennec, Gaël Nicolas, Ganesh Chauhan, David Wallon, Stéphane Rousseau, Anne Claire Richard, Anne Boland, Guillaume Bourque, Hans Markus Munter, Robert Olaso, Vincent Meyer, Adeline Rollin-Sillaire, Florence Pasquier, Luc Letenneur, Richard Redon, Jean-François Dartigues, Christophe Tzourio, Thierry Frebourg, Mark Lathrop, Jean-François Deleuze, Didier Hannequin, Emmanuelle Genin, Philippe Amouyel, Stéphanie Debette, Jean-Charles Lambert, Dominique Campion
We performed whole-exome and whole-genome sequencing in 927 late-onset Alzheimer disease (LOAD) cases, 852 early-onset AD (EOAD) cases, and 1273 controls from France. We assessed the evidence for gene-based association of rare variants with AD in 6 genes for which an association with such variants was previously claimed. When aggregating protein-truncating and missense-predicted damaging variants, we found exome-wide significant association between EOAD risk and rare variants in SORL1, TREM2, and ABCA7. No exome-wide significant signal was obtained in the LOAD sample, and significance of the order of 10(-6) was observed in the whole AD group for TREM2...
July 14, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28774656/plasma-apolipoprotein-e-levels-and-risk-of-dementia-a-mendelian-randomization-study-of-106-562-individuals
#6
Katrine L Rasmussen, Anne Tybjærg-Hansen, Børge G Nordestgaard, Ruth Frikke-Schmidt
INTRODUCTION: In recent prospective studies, low plasma levels of apolipoprotein E (apoE) are associated with high risk of dementia. Whether this reflects a causal association remains to be established. METHODS: Using a Mendelian randomization approach, we studied 106,562 and 75,260 individuals from the general population in observational and genetic analyses, respectively. RESULTS: In observational analyses risk of Alzheimer disease and all dementia increased stepwise as a function of stepwise lower apoE levels (P for trend, 2 × 10(-17) and 9 × 10(-21))...
July 27, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28770390/genome-wide-significant-replicated-and-functional-risk-variants-for-alzheimer-s-disease
#7
Xiaoyun Guo, Wenying Qiu, Rolando Garcia-Milian, Xiandong Lin, Yong Zhang, Yuping Cao, Yunlong Tan, Zhiren Wang, Jing Shi, Jijun Wang, Dengtang Liu, Lisheng Song, Yifeng Xu, Xiaoping Wang, Na Liu, Tao Sun, Jianming Zheng, Justine Luo, Huihao Zhang, Jianying Xu, Longli Kang, Chao Ma, Kesheng Wang, Xingguang Luo
Genome-wide association studies (GWASs) have reported numerous associations between risk variants and Alzheimer's disease (AD). However, these associations do not necessarily indicate a causal relationship. If the risk variants can be demonstrated to be biologically functional, the possibility of a causal relationship would be increased. In this article, we reviewed all of the published GWASs to extract the genome-wide significant (p < 5×10(-8)) and replicated associations between risk variants and AD or AD-biomarkers...
August 2, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28768149/the-biological-foundation-of-the-genetic-association-of-tomm40-with-late-onset-alzheimer-s-disease
#8
Kahli Zeitlow, Lefko Charlambous, Isaac Ng, Sonal Gagrani, Mirta Mihovilovic, Shuhong Luo, Daniel L Rock, Ann Saunders, Allen D Roses, W Kirby Gottschalk
A variable-length poly-T variant in intron 6 of the TOMM40 gene, rs10524523, is associated with risk and age-of-onset of sporadic (late-onset) Alzheimer's disease. In Caucasians, the three predominant alleles at this locus are Short (S), Long (L) or Very long (VL). On an APOE ε3/3 background, the S/VL and VL/VL genotypes are more protective than S/S. The '523 poly-T has regulatory properties, in that the VL poly-T results in higher expression than the S poly-T in luciferase expression systems. The aim of the current work was to identify effects on cellular bioenergetics of increased TOM40 protein expression...
July 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28767121/combined-association-of-presenilin-1-and-apolipoprotein-e-polymorphisms-with-maternal-meiosis-ii-error-in-down-syndrome-births
#9
Pranami Bhaumik, Priyanka Ghosh, Sujay Ghosh, Eleanor Feingold, Umut Ozbek, Biswanath Sarkar, Subrata Kumar Dey
Alzheimer's disease and Down syndrome often exhibit close association and predictively share common genetic risk-factors. Presenilin-1 (PSEN-1) and Apolipoprotein E (APOE) genes are associated with early and late onset of Alzheimer's disease, respectively. Presenilin -1 is involved in faithful chromosomal segregation. A higher frequency of the APOE ε4 allele has been reported among young mothers giving birth to Down syndrome children. In this study, 170 Down syndrome patients, grouped according to maternal meiotic stage of nondisjunction and maternal age at conception, and their parents were genotyped for PSEN-1 intron-8 and APOE polymorphisms...
July 31, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28761931/unc5c-variants-are-associated-with-cerebral-amyloid-angiopathy
#10
Hyun-Sik Yang, Charles C White, Lori B Chibnik, Hans-Ulrich Klein, Julie A Schneider, David A Bennett, Philip L De Jager
OBJECTIVE: To determine whether common genetic variants in UNC5C, a recently identified late-onset Alzheimer disease (LOAD) dementia susceptibility gene, are associated with AD susceptibility or AD-related clinical/pathologic phenotypes. METHODS: We used data from deceased individuals of European descent who participated in the Religious Orders Study or the Rush Memory and Aging Project (n = 1,288). We examined whether there were associations between single nucleotide polymorphisms (SNPs) within ±100 kb of the UNC5C gene and a diagnosis of AD dementia, global cognitive decline, a pathologic diagnosis of AD, β-amyloid load, neuritic plaque count, diffuse plaque count, paired helical filament tau density, neurofibrillary tangle count, and cerebral amyloid angiopathy (CAA) score...
August 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28761928/familiarity-deficits-in-cognitively-normal-aging-individuals-with-apoe-%C3%AE%C2%B54-a-follow-up-investigation-of-medial-temporal-lobe-structural-correlates
#11
Dorothee Schoemaker, Judes Poirier, D Louis Collins, Serge Gauthier, Jens C Pruessner
INTRODUCTION: The apolipoprotein E ε4 (APOE ε4) allele is a well-documented risk factor for Alzheimer's disease (AD). Accordingly, aging individuals carrying one or more ε4 alleles are at considerably greater risk of developing AD over time. In an effort to characterize early cognitive manifestations of AD, we previously outlined selective deficits in familiarity-based recognition in otherwise asymptomatic carriers of the APOE ε4 allele (Schoemaker et al., 2016). In this follow-up report, we aimed to explore the neural correlates of this selective cognitive impairment...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28750690/increased-a%C3%AE-42-%C3%AE-7-like-nicotinic-acetylcholine-receptor-complex-level-in-lymphocytes-is-associated-with-apolipoprotein-e4-driven-alzheimer-s-disease-pathogenesis
#12
Hoau-Yan Wang, Caryn Trocmé-Thibierge, Andres Stucky, Sanket M Shah, Jessica Kvasic, Amber Khan, Philippe Morain, Isabelle Guignot, Eva Bouguen, Karine Deschet, Maria Pueyo, Elisabeth Mocaer, Pierre-Jean Ousset, Bruno Vellas, Vera Kiyasova
BACKGROUND: The apolipoprotein E ε4 (APOE4) genotype is a prominent late-onset Alzheimer's disease (AD) risk factor. ApoE4 disrupts memory function in rodents and may contribute to both plaque and tangle formation. METHODS: Coimmunoprecipitation and Western blot detection were used to determine: 1) the effects of select fragments from the apoE low-density lipoprotein (LDL) binding domain and recombinant apoE subtypes on amyloid beta (Aβ)42-α7 nicotinic acetylcholine receptor (α7nAChR) interaction and tau phosphorylation in rodent brain synaptosomes; and 2) the level of Aβ42-α7nAChR complexes in matched controls and patients with mild cognitive impairment (MCI) and dementia due to AD with known APOE genotypes...
July 27, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28747136/the-relationship-between-apolipoprotein-%C3%AE%C2%B54-carrier-status-and-sleep-characteristics-in-cognitively-normal-older-adults
#13
Melike Kahya, Eric Vidoni, Jeffrey M Burns, Ashley N Thompson, Kayla Meyer, Catherine F Siengsukon
The apolipoprotein (APOE) ε4 allele, a well-described genetic risk factor for late-onset Alzheimer disease (AD), is associated with sleep disturbances even in cognitively normal older adults, although it is not clear whether this association is independent of sleep apnea. We sought to extend previous studies by examining whether cognitively normal older adults without self-reported sleep apnea who carry the APOE ε4 allele have altered sleep characteristics compared to noncarriers. Data from N = 36 (APOE ε4 carriers [n = 9], noncarriers [n = 27]) cognitively normal older adults (Clinical Dementia Rating [CDR] scale = 0) without self-reported sleep apnea were used for these analyses...
January 1, 2017: Journal of Geriatric Psychiatry and Neurology
https://www.readbyqxmd.com/read/28746905/a-pm7-dynamic-residue-ligand-interactions-energy-landscape-of-the-bace1-inhibitory-pathway-by-hydroxyethylamine-compounds-part-i-the-flap-closure-process
#14
Carlos Gueto-Tettay, Alejandro Martinez-Consuegra, Joshua Zuchniarz, Luis Roberto Gueto-Tettay, Juan Carlos Drosos-Ramírez
BACE1 is an enzyme of scientific interest because it participates in the progression of Alzheimer's disease. Hydroxyethylamines (HEAs) are a family of compounds which exhibit inhibitory activity toward BACE1 at a nanomolar level, favorable pharmacokinetic properties and oral bioavailability. The first step in the inhibition of BACE1 by HEAs consists of their entrance into the protease active site and the resultant conformational change in the protein, from Apo to closed form. These two conformations differ in the position of an antiparallel loop (called the flap) which covers the entrance to the catalytic site...
July 14, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28744113/apolipoprotein-%C3%AE%C2%B57-allele-in-memory-complaints-insights-through-protein-structure-prediction
#15
Young Chul Youn, Yong Kwan Lim, Su-Hyun Han, Vo Van Giau, Mi-Kyung Lee, Kwang-Yeol Park, SangYun Kim, Eva Bagyinszky, Seong Soo A An, Hye Ryoun Kim
PURPOSE: APOE ε7 gene is a rare mutant form of APOE ε3. The mutation occurs in the lipid-binding domain of APOE. Based on the protein's structure, APOE ε7 is expected to function in lipid and β-amyloid metabolism, similar to APOE ε4. However, unlike that for APOE ε4, the mechanisms responsible for Alzheimer's disease (AD) cases associated with APOE ε7 expression have not been elucidated. The present study aims to investigate the association between APOE ε7 expression and cognitive impairment...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28741672/finding-of-increased-caudate-nucleus-in-patients-with-alzheimer-s-disease
#16
K Persson, V D Bohbot, N Bogdanovic, G Selbaek, A Braekhus, K Engedal
OBJECTIVES: A recently published study using an automated MRI volumetry method (NeuroQuant®) unexpectedly demonstrated larger caudate nucleus volume in patients with Alzheimer's disease dementia (AD) compared to patients with subjective and mild cognitive impairment (SCI and MCI). The aim of this study was to explore this finding. MATERIALS & METHODS: The caudate nucleus and the hippocampus volumes were measured (both expressed as ratios of intracranial volume) in a total of 257 patients with SCI and MCI according to the Winblad criteria and AD according to ICD-10 criteria...
July 25, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28734699/an-update-on-the-genetics-of-dementia-with-lewy-bodies
#17
REVIEW
Leonie J M Vergouw, Inger van Steenoven, Wilma D J van de Berg, Charlotte E Teunissen, John C van Swieten, Vincenzo Bonifati, Afina W Lemstra, Frank Jan de Jong
The genetic architecture of dementia with Lewy bodies (DLB) is increasingly taking shape. Initially, genetic research focused mainly on linkage and candidate gene studies in small series of DLB patients. More recently, association and exome sequencing studies in larger groups have been conducted, and have shown that several variants in GBA and the APOE ε4 allele are important genetic risk factors for DLB. However, genetic research in DLB is still in its infancy. So far, many genetic studies have been biased and performed in clinically and pathologically heterogeneous populations...
July 13, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28733959/increasing-precision-of-clinical-diagnosis-of-alzheimer-s-disease-using-a-combined-algorithm-incorporating-clinical-and-novel-biomarker-data
#18
REVIEW
Marwan N Sabbagh, Lih-Fen Lue, Daniel Fayard, Jiong Shi
Establishing the in vivo diagnosis of Alzheimer's disease (AD) or other dementias relies on clinical criteria; however, the accuracy of these criteria can be limited. The diagnostic accuracy is 77% for a clinical diagnosis of AD, even among experts. We performed a review through PubMed of articles related to specific diagnostic modalities, including APOE genotyping, cerebrospinal fluid (CSF) testing, fludeoxyglucose F 18 positron emission tomography (PET), amyloid PET, tau PET, computed tomography (CT), single-photon emission CT, magnetic resonance imaging (MRI), and B12 and thyroid-stimulating hormone screening, to determine the specificity and sensitivity of each test used in the clinical diagnosis of AD...
July 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28733268/carriers-of-an-apolipoprotein-e-epsilon-4-allele-are-more-vulnerable-to-a-dietary-deficiency-in-omega-3-fatty-acids-and-cognitive-decline
#19
REVIEW
Tanya Gwendolyn Nock, Raphaël Chouinard-Watkins, Mélanie Plourde
Carriers of an epsilon 4 allele (E4) of apolipoprotein E (APOE) develop Alzheimer's disease (AD) earlier than carriers of other APOE alleles. The metabolism of plasma docosahexaenoic acid (DHA, 22:6n-3), an omega-3 fatty acid (n-3 FA), taken up by the brain and concentrated in neurons, is disrupted in E4 carriers, resulting in lower levels of brain DHA. Behavioural and cognitive impairments have been observed in animals with lower brain DHA levels, with emphasis on loss of spatial memory and increased anxiety...
July 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28731448/left-frontal-hub-connectivity-during-memory-performance-supports-reserve-in-aging-and-mild-cognitive-impairment
#20
Nicolai Franzmeier, Julia C Hartmann, Alexander Nw Taylor, Migeul A Araque Caballero, Lee Simon-Vermot, Katharina Buerger, Lana M Kambeitz-Ilankovic, Birgit Ertl-Wagner, Claudia Mueller, Cihan Catak, Daniel Janowitz, Robert Stahl, Martin Dichgans, Marco Duering, Michael Ewers
Reserve in aging and Alzheimer's disease (AD) is defined as maintaining cognition at a relatively high level in the presence of neurodegeneration, an ability often associated with higher education among other life factors. Recent evidence suggests that higher resting-state functional connectivity within the frontoparietal control network, specifically the left frontal cortex (LFC) hub, contributes to higher reserve. Following up these previous resting-state fMRI findings, we probed memory-task related functional connectivity of the LFC hub as a neural substrate of reserve...
July 17, 2017: Journal of Alzheimer's Disease: JAD
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