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Alzheimer apoe

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https://www.readbyqxmd.com/read/28930663/the-trem2-apoe-pathway-drives-the-transcriptional-phenotype-of-dysfunctional-microglia-in-neurodegenerative-diseases
#1
Susanne Krasemann, Charlotte Madore, Ron Cialic, Caroline Baufeld, Narghes Calcagno, Rachid El Fatimy, Lien Beckers, Elaine O'Loughlin, Yang Xu, Zain Fanek, David J Greco, Scott T Smith, George Tweet, Zachary Humulock, Tobias Zrzavy, Patricia Conde-Sanroman, Mar Gacias, Zhiping Weng, Hao Chen, Emily Tjon, Fargol Mazaheri, Kristin Hartmann, Asaf Madi, Jason D Ulrich, Markus Glatzel, Anna Worthmann, Joerg Heeren, Bogdan Budnik, Cynthia Lemere, Tsuneya Ikezu, Frank L Heppner, Vladimir Litvak, David M Holtzman, Hans Lassmann, Howard L Weiner, Jordi Ochando, Christian Haass, Oleg Butovsky
Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders. We identified a specific apolipoprotein E (APOE)-dependent molecular signature in microglia from models of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer's disease (AD) and in microglia surrounding neuritic β-amyloid (Aβ)-plaques in the brains of people with AD. The APOE pathway mediated a switch from a homeostatic to a neurodegenerative microglia phenotype after phagocytosis of apoptotic neurons...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930654/a-tale-of-two-genes-microglial-apoe-and-trem2
#2
Anna A Pimenova, Edoardo Marcora, Alison M Goate
Microglial cell function is implicated in the etiology of Alzheimer's disease by human genetics. In this issue of Immunity, Krasemann et al. (2017) describe a gene expression signature associated with an APOE- and TREM2-dependent response of microglia to brain tissue damage that accumulates in aging and disease, defining an axis that might be amenable to therapeutic targeting.
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28920073/design-of-pilot-studies-to-inform-the-construction-of-composite-outcome-measures
#3
Steven D Edland, M Colin Ard, Weiwei Li, Lingjing Jiang
BACKGROUND: Composite scales have recently been proposed as outcome measures for clinical trials. For example, the Prodromal Alzheimer's Cognitive Composite (PACC) is the sum of z-score normed component measures assessing episodic memory, timed executive function, and global cognition. Alternative methods of calculating composite total scores using the weighted sum of the component measures that maximize signal-to-noise of the resulting composite score have been proposed. Optimal weights can be estimated from pilot data, but it is an open question how large a pilot trial is required to calculate reliably optimal weights...
June 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28915562/detecting-the-genetic-link-between-alzheimer-s-disease-and-obesity-using-bioinformatics-analysis-of-gwas-data
#4
Qi-Shuai Zhuang, Hao Zheng, Xiao-Dan Gu, Liang Shen, Hong-Fang Ji
Alzheimer's disease (AD) represents the major form of dementia in the elderly. In recent years, accumulating evidence indicate that obesity may act as a risk factor for AD, while the genetic link between the two conditions remains unclear. This bioinformatics analysis aimed to detect the genetic link between AD and obesity on single nucleotide polymorphisms (SNPs), gene, and pathway levels based on genome-wide association studies data. A total of 31 SNPs were found to be shared by AD and obesity, which were linked to 7 genes...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903738/a-randomized-controlled-trial-of-physical-activity-with-individual-goal-setting-and-volunteer-mentors-to-overcome-sedentary-lifestyle-in-older-adults-at-risk-of-cognitive-decline-the-indigo-trial-protocol
#5
Kay L Cox, Elizabeth V Cyarto, Christopher Etherton-Beer, Kathryn A Ellis, Helman Alfonso, Linda Clare, Danny Liew, David Ames, Leon Flicker, Osvaldo P Almeida, Dina LoGiudice, Nicola T Lautenschlager
BACKGROUND: Increasing physical activity (PA) effectively in those who are inactive is challenging. For those who have subjective memory complaints (SMC) or mild cognitive impairment (MCI) this is a greater challenge necessitating the need for more engaging and innovative approaches. The primary aim of this trial is to determine whether a home-based 6-month PA intervention with individual goal-setting and peer mentors (GM-PA) can significantly increase PA levels in insufficiently active older adults at increased risk of developing Alzheimer's disease (AD)...
September 13, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/28900374/association-between-polymorphisms-in-the-promoter-region-of-the-apolipoprotein-e-apoe-gene-and-alzheimer-s-disease-a-meta-analysis
#6
Hanyan Xiao, Yifeng Gao, Lei Liu, Yan Li
Several studies have evaluated the role of polymorphisms in the promoter region of APOE gene that encodes apolipoprotein E (APOE) and the susceptibility to Alzheimer's disease (AD). The aim of this literature review and meta-analysis was to investigate the relationship between the APOE promoter region single nucleotide polymorphisms (SNPs) (rs449647, -491A/T; rs769446, -427T/C and rs405509 -219T/G) and the risk of developing AD. Eligible controlled studies published up to November 2016 were retrieved from main online scientific and medical databases...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28900205/apoe4-associated-phospholipid-dysregulation-contributes-to-development-of-tau-hyper-phosphorylation-after-traumatic-brain-injury
#7
Jiqing Cao, Farida El Gaamouch, James S Meabon, Kole D Meeker, Li Zhu, Margaret B Zhong, John Bendik, Gregory Elder, Ping Jing, Jiahong Xia, Wenjie Luo, David G Cook, Dongming Cai
The apolipoprotein E4 (ApoE4) genotype combines with traumatic brain injury (TBI) to increase the risk of developing Alzheimer's Disease (AD). However, the underlying mechanism(s) is not well-understood. We found that after exposure to repetitive blast-induced TBI, phosphoinositol biphosphate (PIP2) levels in hippocampal regions of young ApoE3 mice were elevated and associated with reduction in expression of a PIP2 degrading enzyme, synaptojanin 1 (synj1). In contrast, hippocampal PIP2 levels in ApoE4 mice did not increase after blast TBI...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899010/modelling-apoe-%C3%A9-3-4-allele-associated-sporadic-alzheimer-s-disease-in-an-induced-neuron
#8
Hongwon Kim, Junsang Yoo, Jaein Shin, Yujung Chang, Junghyun Jung, Dong-Gyu Jo, Janghwan Kim, Wonhee Jang, Christopher J Lengner, Byung-Soo Kim, Jongpil Kim
The recent generation of induced neurons by direct lineage conversion holds promise for in vitro modelling of sporadic Alzheimer's disease. Here, we report the generation of induced neuron-based model of sporadic Alzheimer's disease in mice and humans, and used this system to explore the pathogenic mechanisms resulting from the sporadic Alzheimer's disease risk factor apolipoprotein E (APOE) ɛ3/4 allele. We show that mouse and human induced neurons overexpressing mutant amyloid precursor protein in the background of APOE ɛ3/4 allele exhibit altered amyloid precursor protein (APP) processing, abnormally increased production of amyloid-β42 and hyperphosphorylation of tau...
August 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28893185/factors-that-influence-the-levels-of-cerebrospinal-fluid-biomarkers-in-memory-clinic-patients
#9
Anne-Brita Knapskog, Rannveig Sakshaug Eldholm, Anne Braekhus, Knut Engedal, Ingvild Saltvedt
BACKGROUND: The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ), phospho tau (P-tau) and total tau (T-tau) are used increasingly to support a clinical diagnosis of Alzheimer's disease. The diagnostic power of these biomarkers has been reported to vary among different studies' results. The results are poorer when heterogeneous groups of patients have been included compared to studies where patients with Alzheimer's dementia (AD) and healthy controls have been studied. The aim of this study was to examine if age, APOE genotype and sex were associated with the levels of CSF biomarkers among patients referred to a memory clinic...
September 11, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/28888721/tmem106b-and-apoe-polymorphisms-in-chmp2b-mediated-frontotemporal-dementia-ftd-3
#10
Nina Rostgaard, Peter Roos, Esben Budtz-Jørgensen, Peter Johannsen, Gunhild Waldemar, Anne Nørremølle, Suzanne G Lindquist, Susanne Gydesen, Jeremy M Brown, John Collinge, Adrian M Isaacs, Troels T Nielsen, Jørgen E Nielsen
Single-nucleotide polymorphisms in the TMEM106B gene have been identified as a risk factor in frontotemporal dementia (FTD). The major allele of SNP rs3173615 is a risk factor in sporadic FTD, whereas the minor allele seems protective in GRN- and C9orf72-mediated FTD. The role of apolipoprotein E (ApoE) in FTD is uncertain, though an established risk factor in Alzheimer's disease. In a unique Danish family, inherited FTD is caused by a mutation in the CHMP2B gene located on chromosome 3 (FTD-3). In this family, both risk factors TMEM106B and ApoE were analyzed and correlated to age at onset (AAO) and progression in terms of age at institutionalization (AAI) and age at death (AAD)...
July 11, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28884572/nanobody-based-apolipoprotein-e-immunosensor-for-point-of-care-testing
#11
Xiang Ren, Junrong Yan, Dan Wu, Qin Wei, Yakun Wan
Alzheimer's disease (AD) biomarkers can reflect the neurochemical indicators used to estimate the risk in clinical nephrology. Apolipoprotein E (ApoE) is an early biomarker for AD in clinical diagnosis. In this research, through bactrian camel immunization, lymphocyte isolation, RNA extraction, and library construction, ApoE-specific Nbs with high affinity were successfully separated from an immune phage display nanobody library. Herein, a colorimetric immunosensor was developed for the point-of-care testing of ApoE by layer-by-layer nanoassembly techniques and novel nanobodies (Nbs)...
September 11, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28879085/progressive-medial-temporal-lobe-atrophy-during-preclinical-alzheimer-s-disease
#12
Corinne Pettigrew, Anja Soldan, Kelly Sloane, Qing Cai, Jiangxia Wang, Mei-Cheng Wang, Abhay Moghekar, Michael I Miller, Marilyn Albert
This study examined whether longitudinal MRI trajectories in medial temporal lobe (MTL) brain regions differed among groups of cognitively normal individuals defined by their cerebrospinal fluid (CSF) levels when they were first enrolled (N = 207; mean clinical follow-up = 13.3 years (max = 20 years), mean MRI follow-up = 2.4 years (max = 8 years)). We first compared atrophy rates among groups defined by CSF amyloid and phosphorylated-tau (p-tau) vs. CSF amyloid and total tau (t-tau). We also examined whether, in the presence of amyloid or tau/p-tau, the atrophy rates differed based on whether the subjects ultimately progressed to a diagnosis of mild cognitive impairment (MCI), as well as whether apolipoprotein ε4 (Apoε4) status had an impact on the longitudinal MRI trajectories...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28879083/monitoring-disease-progression-in-mild-cognitive-impairment-associations-between-atrophy-patterns-cognition-apoe-and-amyloid
#13
Farshad Falahati, Daniel Ferreira, J-Sebastian Muehlboeck, Maria Eriksdotter, Andrew Simmons, Lars-Olof Wahlund, Eric Westman
BACKGROUND: A disease severity index (SI) for Alzheimer's disease (AD) has been proposed that summarizes MRI-derived structural measures into a single score using multivariate data analysis. OBJECTIVES: To longitudinally evaluate the use of the SI to monitor disease progression and predict future progression to AD in mild cognitive impairment (MCI). Further, to investigate the association between longitudinal change in the SI and cognitive impairment, Apolipoprotein E (APOE) genotype as well as the levels of cerebrospinal fluid amyloid-beta 1-42 (Aβ) peptide...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28874525/differential-diagnosis-of-alzheimer-s-disease-using-spectrochemical-analysis-of-blood
#14
Maria Paraskevaidi, Camilo L M Morais, Kássio M G Lima, Julie S Snowden, Jennifer A Saxon, Anna M T Richardson, Matthew Jones, David M A Mann, David Allsop, Pierre L Martin-Hirsch, Francis L Martin
The progressive aging of the world's population makes a higher prevalence of neurodegenerative diseases inevitable. The necessity for an accurate, but at the same time, inexpensive and minimally invasive, diagnostic test is urgently required, not only to confirm the presence of the disease but also to discriminate between different types of dementia to provide the appropriate management and treatment. In this study, attenuated total reflection FTIR (ATR-FTIR) spectroscopy combined with chemometric techniques were used to analyze blood plasma samples from our cohort...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28863046/cognitive-aging-in-black-and-white-americans-cognition-cognitive-decline-and-incidence-of-alzheimer-disease-dementia
#15
Jennifer Weuve, Lisa L Barnes, Carlos F Mendes de Leon, Kumar B Rajan, Todd Beck, Neelum T Aggarwal, Liesi E Hebert, David A Bennett, Robert S Wilson, Denis A Evans
BACKGROUND: US-based studies have reported that older blacks perform worse than older whites on cognitive tests and have higher risk of Alzheimer disease dementia (AD). It is unclear whether these findings reflect differences in cognitive decline. METHODS: The Chicago Health and Aging Project followed individuals, 65+ years old (64% black, 36% white), for up to 18 years. Participants underwent triennial cognitive assessments; stratified randomized samples underwent assessments for AD...
August 31, 2017: Epidemiology
https://www.readbyqxmd.com/read/28859660/early-versus-late-onset-alzheimer-s-disease-in-clinical-practice-cognitive-and-global-outcomes-over-3%C3%A2-years
#16
Carina Wattmo, Åsa K Wallin
BACKGROUND: Whether age at onset influences Alzheimer's disease (AD) progression and the effectiveness of cholinesterase inhibitor (ChEI) therapy is not clear. We aimed to compare longitudinal cognitive and global outcomes in ChEI-treated patients with early-onset Alzheimer's disease (EOAD) versus late-onset Alzheimer's disease (LOAD) in clinical practice. METHODS: This 3-year, prospective, observational, multicentre study included 1017 participants with mild to moderate AD; 143 had EOAD (age at onset < 65 years) and 874 had LOAD (age at onset ≥ 65 years)...
August 31, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28855124/towards-a-routine-application-of-top-down-approaches-for-label-free-discovery-workflows
#17
Pierre-Olivier Schmit, Jerome Vialaret, Hans J C T Wessels, Alain Van Gool, Christophe Hirtz, Sylvain Lehmann, Audrey Gabelle, Jason Wood, Marshall Bern, Rainer Paape, Detlev Suckau, Gary Kruppa, Christophe Hirtz
Thanks to proteomics investigations, our vision of the role of different protein isoforms in the pathophysiology of diseases has largely evolved. The idea that protein biomarkers like tau, amyloid peptides, ApoE, cystatin, or neurogranin are represented in body fluids as single species is obviously over-simplified, as most proteins are present in different isoforms and subjected to numerous processing and post-translational modifications. Measuring the intact mass of proteins by MS has the advantage to provide information on the presence and relative amount of the different proteoforms...
August 27, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28852706/ultra-rare-mutations-in-srcap-segregate-in-caribbean-hispanic-families-with-alzheimer-disease
#18
Badri N Vardarajan, Giuseppe Tosto, Roger Lefort, Lei Yu, David A Bennett, Philip L De Jager, Sandra Barral, Dolly Reyes-Dumeyer, Peter L Nagy, Joseph H Lee, Rong Cheng, Martin Medrano, Rafael Lantigua, Ekaterina Rogaeva, Peter St George-Hyslop, Richard Mayeux
OBJECTIVE: To identify rare coding variants segregating with late-onset Alzheimer disease (LOAD) in Caribbean Hispanic families. METHODS: Whole-exome sequencing (WES) was completed in 110 individuals from 31 Caribbean Hispanic families without APOE ε4 homozygous carriers. Rare coding mutations segregating in families were subsequently genotyped in additional families and in an independent cohort of Caribbean Hispanic patients and controls. SRCAP messenger RNA (mRNA) expression was assessed in whole blood from mutation carriers with LOAD, noncarriers with LOAD, and healthy elderly controls, and also from autopsied brains in 2 clinical neuropathologic cohort studies of aging and dementia...
October 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28846757/apolipoprotein-e-genotype-and-sex-risk-factors-for-alzheimer-disease-a-meta-analysis
#19
Scott C Neu, Judy Pa, Walter Kukull, Duane Beekly, Amanda Kuzma, Prabhakaran Gangadharan, Li-San Wang, Klaus Romero, Stephen P Arneric, Alberto Redolfi, Daniele Orlandi, Giovanni B Frisoni, Rhoda Au, Sherral Devine, Sanford Auerbach, Ana Espinosa, Mercè Boada, Agustín Ruiz, Sterling C Johnson, Rebecca Koscik, Jiun-Jie Wang, Wen-Chuin Hsu, Yao-Liang Chen, Arthur W Toga
Importance: It is unclear whether female carriers of the apolipoprotein E (APOE) ε4 allele are at greater risk of developing Alzheimer disease (AD) than men, and the sex-dependent association of mild cognitive impairment (MCI) and APOE has not been established. Objective: To determine how sex and APOE genotype affect the risks for developing MCI and AD. Data Sources: Twenty-seven independent research studies in the Global Alzheimer's Association Interactive Network with data on nearly 58 000 participants...
August 28, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28833437/increased-n200-and-p300-latencies-in-cognitively-impaired-elderly-carrying-apoe-%C3%AE%C2%B5-4-allele
#20
Marco Túlio Gualberto Cintra, Rafaela Teixeira Ávila, Thayana Oliveira Soares, Luciana Cristina Matos Cunha, Katia Daniela Silveira, Edgar Nunes de Moraes, Kaique Roger Simas, Renato Bragança Fernandes, Denise Utsch Gonçalves, Nilton Alves de Rezende, Maria Aparecida Camargos Bicalho
OBJECTIVE: To compare the results of neuropsychological tests, evoked potentials N200 and P300 and polymorphisms of ApoE and BDNF rs6265 between patients with normal cognition and those with mild cognitive impairment (MCI) and Alzheimer's dementia (AD). METHODS: This is a cross-sectional study of elderly individuals with normal cognition and those with MCI and AD, who were submitted to evoked potential tests (N200 and P300) by means of hearing stimuli based on the auditory oddball paradigm...
August 22, 2017: International Journal of Geriatric Psychiatry
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