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Apo E4

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https://www.readbyqxmd.com/read/28920073/design-of-pilot-studies-to-inform-the-construction-of-composite-outcome-measures
#1
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/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
#2
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/28900205/apoe4-associated-phospholipid-dysregulation-contributes-to-development-of-tau-hyper-phosphorylation-after-traumatic-brain-injury
#3
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/28844148/the-association-of-apolipoprotein-e-gene-polymorphism-with-cognitive-performance-in-nondemented-polish-adults-aged-55-to-75
#4
Małgorzata T Piskunowicz, Katarzyna Linkowska, Szymon Gołota, Tomasz Grzybowski, Kornelia Kędziora-Kornatowska, Alina Borkowska
The ε4 allele of the apolipoprotein E (APOE) gene is known as a risk factor for dementia. How APOE ε polymorphism affects cognitive performance in nondemented aging subjects remains less clear. In this study, the relationship between APOE status and cognitive performance across various cognitive domains in adults aged 55 to 75 years ( n = 74) without dementia was investigated. E4 carriers ( n = 11) performed worse versus noncarriers on forward Digit Span and delayed recall of the Rey-Osterrieth complex figure...
January 1, 2017: International Journal of Aging & Human Development
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
#5
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/28800603/genetic-variants-specific-to-aging-related-verbal-memory-insights-from-gwass-in-a-population-based-cohort
#6
Thalida E Arpawong, Neil Pendleton, Krisztina Mekli, John J McArdle, Margaret Gatz, Chris Armoskus, James A Knowles, Carol A Prescott
Verbal memory is typically studied using immediate recall (IR) and delayed recall (DR) scores, although DR is dependent on IR capability. Separating these components may be useful for deciphering the genetic variation in age-related memory abilities. This study was conducted to (a) construct individual trajectories in IR and independent aspects of delayed recall, or residualized-DR (rDR), across older adulthood; and (b) identify genetic markers that contribute to four estimated phenotypes: IR and rDR levels and changes after age 60...
2017: PloS One
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
#7
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/28751738/apoe-influences-the-blood-brain-barrier-through-the-nf-%C3%AE%C2%BAb-mmp-9-pathway-after-traumatic-brain-injury
#8
Zhipeng Teng, Zongduo Guo, Jianjun Zhong, Chongjie Cheng, Zhijian Huang, Yue Wu, Shuang Tang, Chao Luo, Xing Peng, Haitao Wu, Xiaochuan Sun, Li Jiang
Apolipoprotein E (ApoE), encoded by the ApoE gene (APOE), influences the outcomes of traumatic brain injury (TBI), but the mechanism remains unclear. The present study aimed to investigate the effects of different ApoEs on the outcome of TBI and to explore the possible mechanisms. Controlled cortical impact (CCI) was performed on APOEε3 (E3) and APOEε4 (E4) transgenic mice, APOE-KO (KO) mice, and wild type (WT) mice to construct an in vivo TBI model. Neurological deficits, blood brain barrier (BBB) permeability and brain edema were detected at days 1, 3, and 7 after TBI...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28750833/putting-attention-in-the-spotlight-the-influence-of-apoe-genotype-on-visual-search-in-mid-adulthood
#9
Claire Lancaster, Sophie Forster, Naji Tabet, Jennifer Rusted
The Apolipoprotein E e4 allele is associated with greater cognitive decline with age, yet effects of this gene are also observed earlier in the lifespan. This research explores genotype differences (e2, e3, e4) in the allocation of visuospatial attention in mid-adulthood. Sixty-six volunteers, aged 45-55 years, completed two paradigms probing the active selection of information at the focus of attention (a dynamic scaling task) and perceptual capacity differences. Two methods of statistical comparison (parametric statistics, Bayesian inference) found no significant difference between e4 carriers and the homozygous e3 group on either the dynamic scaling or perceptual load task...
July 25, 2017: Behavioural Brain Research
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
#10
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/28741672/finding-of-increased-caudate-nucleus-in-patients-with-alzheimer-s-disease
#11
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/28740125/apoe-genotype-influences-insulin-resistance-apolipoprotein-cii-and-ciii-according-to-plasma-fatty-acid-profile-in-the-metabolic-syndrome
#12
Rosalind Fallaize, Andrew L Carvalho-Wells, Audrey C Tierney, Carmen Marin, Beata Kieć-Wilk, Aldona Dembińska-Kieć, Christian A Drevon, Catherine DeFoort, José Lopez-Miranda, Ulf Risérus, Wim H Saris, Ellen E Blaak, Helen M Roche, Julie A Lovegrove
Metabolic markers associated with the Metabolic Syndrome (MetS) may be affected by interactions between the APOE genotype and plasma fatty acids (FA). In this study, we explored FA-gene interactions between the missense APOE polymorphisms and FA status on metabolic markers in MetS. Plasma FA, blood pressure, insulin sensitivity and lipid concentrations were determined at baseline and following a 12-week randomized, controlled, parallel, dietary FA intervention in 442 adults with MetS (LIPGENE study). FA-APOE gene interactions at baseline and following change in plasma FA were assessed using adjusted general linear models...
July 24, 2017: Scientific Reports
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
#13
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...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28731446/effect-of-apoe-genotype-on-synaptic-proteins-in-earlier-adult-life
#14
Lindsey I Sinclair, Seth Love
BACKGROUND: Possession of APOEɛ4 is a strong risk factor for late-onset Alzheimer's disease and is associated with loss of synaptic proteins in the elderly even in the absence of Alzheimer's disease. OBJECTIVE: We hypothesized that ɛ4 allele possession in non-demented adults aged under-75 would also be associated with alterations in the levels of synaptic proteins. METHODS: We measured synaptophysin, PSD95, drebrin, SNAP-25, and septin 7 by ELISA in hippocampus and superior temporal gyrus from 103 adults aged <75 without dementia...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731444/the-relationship-of-brain-amyloid-load-and-apoe-status-to-regional-cortical-thinning-and-cognition-in-the-adni-cohort
#15
Chunfei Li, David A Loewenstein, Ranjan Duara, Mercedes Cabrerizo, Warren Barker, Malek Adjouadi
BACKGROUND: Both amyloid (Aβ) load and APOE4 allele are associated with neurodegenerative changes in Alzheimer's disease (AD) prone regions and with risk for cognitive impairment. OBJECTIVE: To evaluate the unique and independent contribution of APOE4 allele status (E4+∖E4-), Aβ status (Amy+∖Amy-), and combined APOE4 and Aβ status on regional cortical thickness (CoTh) and cognition among participants diagnosed as cognitively normal (CN, n = 251), early mild cognitive impairment (EMCI, n = 207), late mild cognitive impairment (LMCI, n = 196), and mild AD (n = 162) from the ADNI...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731260/transcriptional-regulation-of-app-by-apoe-to-boldly-go-where-no-isoform-has-gone-before-apoe-app-transcription-and-ad-hypothesised-mechanisms-and-existing-knowledge-gaps
#16
REVIEW
Liying Corinne Lee, Michele Q L Goh, Edward H Koo
Alzheimer's disease (AD) is the most common form of dementia that gradually disrupts the brain network to impair memory, language and cognition. While the amyloid hypothesis remains the leading proposed mechanism to explain AD pathophysiology, anti-amyloid therapeutic strategies have yet to translate into useful therapies, suggesting that amyloid β-protein and its precursor, the amyloid precursor protein (APP) are but a part of the disease cascade. Further, risk of AD can be modulated by a number of factors, the most impactful being the ɛ4 isoform of apolipoprotein E (apoE)...
September 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28726810/a-randomized-controlled-trial-of-disclosing-genetic-risk-information-for-alzheimer-disease-via-telephone
#17
Kurt D Christensen, Wendy R Uhlmann, J Scott Roberts, Erin Linnenbringer, Peter J Whitehouse, Charmaine D M Royal, Thomas O Obisesan, L Adrienne Cupples, Melissa B Butson, Grace-Ann Fasaye, Susan Hiraki, Clara A Chen, Uwe Siebert, Robert Cook-Deegan, Robert C Green
PurposeTelephone disclosure of genetic test results can improve access to services. To date, studies of its impact have focused on return of Mendelian risk information, principally hereditary cancer syndromes.MethodsIn a multisite trial of Alzheimer disease genetic risk disclosure, asymptomatic adults were randomized to receive test results in person or via telephone. Primary analyses examined patient outcomes 12 months after disclosure.ResultsData from 257 participants showed that telephone disclosure occurred 7...
July 20, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28707482/peripheral-inflammation-apolipoprotein-e4-and-amyloid-%C3%AE-interact-to-induce-cognitive-and-cerebrovascular-dysfunction
#18
Felecia M Marottoli, Yuriko Katsumata, Kevin P Koster, Riya Thomas, David W Fardo, Leon M Tai
Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer's disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 ( APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated. The goal of this study was to determine the interactive effect of APOE4, Aβ, and chronic repeated peripheral inflammation on cerebrovascular and cognitive dysfunction in vivo...
July 2017: ASN Neuro
https://www.readbyqxmd.com/read/28705029/bosnian-study-of-apoe-distribution-bosad-a-comparison-with-other-european-populations
#19
Grażyna Adler, Mateusz A Adler, Anna Urbańska, Karolina Skonieczna-Żydecka, Emina Kiseljakovic, Amina Valjevac, Miłosz Parczewski, Almira Hadzovic-Dzuvo
BACKGROUND: The ε2, ε3 and ε4 alleles of APOE gene have been associated with several diseases in different populations. Data on the frequency of alleles are used in both a clinical and evolutionary context. Although the data on frequency of these alleles are numerous, there are no reports for the population of Bosnia and Herzegovina. AIM: To estimate the frequency of APOE alleles in a healthy Bosnian population and compare it to data for other European populations...
July 13, 2017: Annals of Human Biology
https://www.readbyqxmd.com/read/28684412/isoform-and-cell-type-specific-structure-of-apolipoprotein-e-lipoparticles-as-revealed-by-a-novel-forster-resonance-energy-transfer-assay
#20
Eleanna Kara, Jordan D Marks, Zhanyun Fan, Jacob A Klickstein, Allyson D Roe, Kelly A Krogh, Susanne Wegmann, Masato Maesako, Christina C Luo, Ravi Mylvaganam, Oksana Berezovska, Eloise Hudry, Bradley T Hyman
Apolipoprotein E (apoE) has an important role in the pathogenesis of Alzheimer's disease with its three isoforms having distinct effects on disease risk. Here, we assessed the conformational differences between those isoforms using a novel flow cytometry-Forster resonance energy transfer (FRET) assay. We showed that the conformation of intracellular apoE within HEK cells and astrocytes adopts a directional pattern; in other words, E4 adopts the most closed conformation, E2 adopts the most open conformation, and E3 adopts an intermediate conformation...
September 8, 2017: Journal of Biological Chemistry
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