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Apo E4

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https://www.readbyqxmd.com/read/28634550/sortilin-related-receptor-expression-in-human-neural-stem-cells-derived-from-alzheimer-s-disease-patients-carrying-the-apoe-epsilon-4-allele
#1
Alen Zollo, Zoe Allen, Helle F Rasmussen, Filomena Iannuzzi, Yichen Shi, Agnete Larsen, Thorsten J Maier, Carmela Matrone
Alzheimer's disease (AD) is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4) allele. Changes in amyloid precursor protein (APP) binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ) peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1) as an important factor in APP trafficking and processing...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28634213/omega-3-fatty-acids-increase-the-unfolded-protein-response-and-improve-amyloid-%C3%AE-phagocytosis-by-macrophages-of-patients-with-mild-cognitive-impairment
#2
Henry M Olivera-Perez, Larry Lam, Johnny Dang, Weilan Jiang, Fabian Rodriguez, Elizabeth Rigali, Sarah Weitzman, Verna Porter, Liudmilla Rubi, Marco Morselli, Matteo Pellegrini, Milan Fiala
Mϕs of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ. ω-3 in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI. Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1...
June 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28614836/visual-evaluation-of-medial-temporal-lobe-atrophy-as-a-clinical-marker-of-conversion-from-mild-cognitive-impairment-to-dementia-and-for-predicting-progression-in-patients-with-mild-cognitive-impairment-and-mild-alzheimer-s-disease
#3
Karin Persson, Maria Lage Barca, Rannveig Sakshaug Eldholm, Lena Cavallin, Jūratė Šaltytė Benth, Geir Selbæk, Anne Brækhus, Ingvild Saltvedt, Knut Engedal
BACKGROUND/AIMS: To evaluate whether visual assessment of medial temporal lobe atrophy (vaMTA) can predict 2-year conversion from mild cognitive impairment (MCI) to dementia and progression of MCI and Alzheimer's disease dementia as measured by the Clinical Dementia Rating Scale Sum of Boxes score (CDR-SB). METHODS: vaMTA was performed in 94 patients with MCI according to the Winblad criteria and in 124 patients with AD according to ICD-10 and NINCDS-ADRDA criteria...
June 15, 2017: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/28597004/increased-binding-of-apolipoproteins-a-i-and-e4-to-triglyceride-rich-lipoproteins-is-linked-to-induction-of-hypertriglyceridemia
#4
Irina N Gorshkova, David Atkinson
Hypertriglyceridemia (HTG) is an independent factor of atherosclerotic cardiovascular disease and a hallmark of many metabolic disorders. However, the molecular etiology of HTG is still largely unknown. In mice, severe HTG may be induced by expression of specific mutants of apolipoprotein (apo) A-I or wild type (WT) apoE4. Expression of a certain apoE4 mutant results in mild HTG, while expression of another apoE4 mutant or WT apoA-I results in normal plasma triglyceride (TG) levels. Biophysical studies of the apoA-I and apoE4 forms associated with HTG help better understand the molecular mechanisms of induction of HTG by these proteins...
2017: JSM Atheroscler
https://www.readbyqxmd.com/read/28596117/disrupted-white-matter-structural-networks-in-healthy-older-adults-apoe-%C3%AE%C2%B54-carriers-an-international-multicenter-dti-study
#5
Enrica Cavedo, Simone Lista, Katrine Rojkova, Patrizia Andrea Chiesa, Marion Houot, Katharina Brueggen, Janusch Blautzik, Arun L W Bokde, Bruno Dubois, Frederik Barkhof, Petra J W Pouwels, Stefan Teipel, Harald Hampel
The ε4 allelic variant of the Apolipoprotein E gene (APOE ε4) is the best-established genetic risk factor for late-onset Alzheimer's disease (AD). White matter (WM) microstructural damages measured with Diffusion Tensor Imaging (DTI) represent an early sign of fiber tract disconnection in AD. We examined the impact of APOEε4 on WM microstructure in elderly individuals from the multicenter European DTI Study on Dementia. Voxelwise statistical analysis of Fractional anisotropy (FA), mean diffusivity, radial and axial diffusivity (MD, radD and axD respectively) was carried out using Tract-Based Spatial Statistics...
June 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28582863/framingham-risk-score-and-the-risk-of-progression-from-mild-cognitive-impairment-to-dementia
#6
Giovanna Viticchi, Lorenzo Falsetti, Laura Buratti, Giulia Sajeva, Simona Luzzi, Marco Bartolini, Leandro Provinciali, Mauro Silvestrini
BACKGROUND: Mild cognitive impairment (MCI) often represents the clinical manifestation of cognitive deterioration preceding Alzheimer's disease (AD). Currently, there are no reliable approaches for an objective evaluation of the risk of developing AD in MCI patients. OBJECTIVE: The aim of this study was to verify whether the Framingham cardiovascular risk profile (FCRP) could be useful to identify patients at the highest risk of conversion from MCI to AD. METHODS: Patients with amnestic MCI (aMCI) were carefully investigated to assess their vascular risk profile...
May 27, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28578665/risk-factors-for-dementia-in-the-ninth-decade-of-life-and-beyond-a-study-of-the-lothian-birth-cohort-1921
#7
Ruth A Sibbett, Tom C Russ, Ian J Deary, John M Starr
BACKGROUND: With increasing numbers of people surviving beyond eighty years, this section of the population demands attention to reduce the impact of dementia. In order to develop effective preventative strategies, it is essential to understand age-specific risk factor profiles for dementia: do risk factors for dementia in those in their sixties and seventies persist into oldest age? The aims of this study were to determine incident dementia and to investigate the risk profile for dementia from age 79 to 95 years in a well-characterised cohort...
June 2, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28569173/apoe-isoforms-differentially-regulates-cleavage-and-secretion-of-bdnf
#8
Abhik Sen, Thomas J Nelson, Daniel L Alkon
Apolipoprotein E4 (ApoE4) is a major genetic risk factor for sporadic or late onset Alzheimer's disease (AD). Brain-derived neurotrophic factor (BDNF) is decreased by 3 to 4-fold in the brains of AD patients at autopsy. ApoE4 mice also have reduced BDNF levels. However, there have been no reports relating the different ApoE isoforms or AD to differential regulation of BDNF. Here we report that in the hippocampal regions of AD patients both prepro-BDNF and pro-BDNF expression showed a 40 and 60% decrease respectively compared to that expression in the hippocampi of age-matched control patients...
June 1, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28550258/effect-of-apoe-genotype-on-amyloid-deposition-brain-volume-and-memory-in-cognitively-normal-older-individuals
#9
Yen Ying Lim, Robert Williamson, Simon M Laws, Victor L Villemagne, Pierrick Bourgeat, Christopher Fowler, Stephanie Rainey-Smith, Olivier Salvado, Ralph N Martins, Christopher C Rowe, Colin L Masters, Paul Maruff
BACKGROUND: The association between the apolipoprotein E (APOE) ɛ4 allele and high risk of developing Alzheimer's disease (AD) dementia before the age of 80 has been recognized for over 30 years. However, the timing and mode of action of APOE is not understood, nor has there been a detailed analysis of the effect of APOE genotype on memory, hippocampal volume, and amyloid-β (Aβ) levels in cognitively normal adults. OBJECTIVE: Examine the effect of APOE allelic genotype on the relationship between Aβ levels, hippocampal volume, and memory in cognitively normal adults...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550244/apoe-%C3%AE%C2%B54-modulation-of-training-outcomes-in-several-cognitive-domains-in-a-sample-of-cognitively-intact-older-adults
#10
Ramón López-Higes, Inmaculada C Rodríguez-Rojo, José M Prados, Pedro Montejo, David Del-Río, María Luisa Delgado-Losada, Mercedes Montenegro, David López-Sanz, Ana Barabash
BACKGROUND: Most research points to the ɛ4 allele of the apolipoprotein E (APOE) gene as the most recognizable genetic risk factor associated with Alzheimer's disease pathogenesis. It has been also suggested that the APOEɛ4 allele has a negative influence on cognitive functioning, which begins long before cognitive impairment becomes manifest. However, still, little is known about the APOEɛ4 interaction with cognitive intervention programs. OBJECTIVE: The main goal of this study was to explore whether there was a differential APOE genotype modulation effect after cognitive training in different domains, such as language comprehension, executive functions, and memory...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28549269/high-hair-cortisol-concentrations-predict-worse-cognitive-outcome-after-stroke-results-from-the-tabasco-prospective-cohort-study
#11
E Ben Assayag, O Tene, A D Korczyn, L Shopin, E Auriel, J Molad, H Hallevi, C Kirschbaum, N M Bornstein, S Shenhar-Tsarfaty, E Kliper, T Stalder
BACKGROUND AND PURPOSE: The role of stress-related endocrine dysregulation in the development of cognitive changes following a stroke needs further elucidation. We explored this issue in a longitudinal study on stroke survivors using hair cortisol concentrations (HCC), a measure of integrated long-term cortisol levels. METHODS: Participants were consecutive cognitively intact first-ever mild-moderate ischemic stroke/transient ischemic attack (TIA) survivors from the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study...
May 18, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28537274/characterization-of-pathogenic-sorl1-genetic-variants-for-association-with-alzheimer-s-disease-a-clinical-interpretation-strategy
#12
Henne Holstege, Sven J van der Lee, Marc Hulsman, Tsz Hang Wong, Jeroen Gj van Rooij, Marjan Weiss, Eva Louwersheimer, Frank J Wolters, Najaf Amin, André G Uitterlinden, Albert Hofman, M Arfan Ikram, John C van Swieten, Hanne Meijers-Heijboer, Wiesje M van der Flier, Marcel Jt Reinders, Cornelia M van Duijn, Philip Scheltens
Accumulating evidence suggests that genetic variants in the SORL1 gene are associated with Alzheimer disease (AD), but a strategy to identify which variants are pathogenic is lacking. In a discovery sample of 115 SORL1 variants detected in 1908 Dutch AD cases and controls, we identified the variant characteristics associated with SORL1 variant pathogenicity. Findings were replicated in an independent sample of 103 SORL1 variants detected in 3193 AD cases and controls. In a combined sample of the discovery and replication samples, comprising 181 unique SORL1 variants, we developed a strategy to classify SORL1 variants into five subtypes ranging from pathogenic to benign...
May 24, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28536518/mri-visual-ratings-of-brain-atrophy-and-white-matter-hyperintensities-across-the-spectrum-of-cognitive-decline-are-differently-affected-by-age-and-diagnosis
#13
Hanneke F M Rhodius-Meester, Marije R Benedictus, Mike P Wattjes, Frederik Barkhof, Philip Scheltens, Majon Muller, Wiesje M van der Flier
Aim: To assess the associations of age and diagnosis with visual ratings of medial temporal lobe atrophy (MTA), parietal atrophy (PA), global cortical atrophy (GCA), and white matter hyperintensities (WMH) and to investigate their clinical value in a large memory clinic cohort. Methods: We included 2,934 patients (age 67 ± 9 years; 1,391 [47%] female; MMSE 24 ± 5) from the Amsterdam Dementia Cohort (1,347 dementia due to Alzheimer's disease [AD]; 681 mild cognitive impairment [MCI]; 906 controls with subjective cognitive decline)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28533891/nuclear-uptake-of-an-amino-terminal-fragment-of-apolipoprotein-e4-promotes-cell-death-and-localizes-within-microglia-of-the-alzheimer-s-disease-brain
#14
Julia E Love, Ryan J Day, Justin W Gause, Raquel J Brown, Xinzhu Pu, Dustin I Theis, Chad A Caraway, Wayne W Poon, Abir A Rahman, Brad E Morrison, Troy T Rohn
Although harboring the apolipoprotein E4 (APOE4) allele is a well known risk factor in Alzheimer's disease (AD), the mechanism by which it contributes to disease risk remains elusive. To investigate the role of proteolysis of apoE4 as a potential mechanism, we designed and characterized a site-directed cleavage antibody directed at position D151 of the mature form of apoE4 and E3. Characterization of this antibody indicated a high specificity for detecting synthesized recombinant proteins corresponding to the amino acid sequences 1-151 of apoE3 and E4 that would generate the 17 kDa (p17) fragment...
2017: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/28528321/omega-3-fatty-acids-lipids-and-apoe-lipidation-in-alzheimer-s-disease-a-rationale-for-multi-nutrient-dementia-prevention
#15
Marcus O Grimm, Daniel Michaelson, Tobias Hartmann
In the last decade it has become obvious that Alzheimer's disease (AD) is closely linked to changes in lipids or lipid metabolism. One of the main pathological hallmarks of AD is amyloid-β (Aβ) deposition. Aβ is derived from sequential proteolytic processing of the amyloid precursor protein (APP). Interestingly, both, the APP and all APP secretases are transmembrane proteins which cleave APP close to and in the lipid bilayer. Moreover, apolipoprotein E4 (apoE4) has been identified as the most prevalent genetic risk factor for AD...
May 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28527212/apolipoprotein-e4-gender-body-mass-index-inflammation-insulin-resistance-and-air-pollution-interactions-recipe-for-alzheimer-s-disease-development-in-mexico-city-young-females
#16
Lilian Calderón-Garcidueñas, Suzanne M de la Monte
Given the epidemiological trends of increasing Alzheimer's disease (AD) and growing evidence that exposure and lifestyle factors contribute to AD risk and pathogenesis, attention should be paid to variables such as air pollution, in order to reduce rates of cognitive decline and dementia. Exposure to fine particulate matter (PM2.5) and ozone (O3) above the US EPA standards is associated with AD risk. Mexico City children experienced pre- and postnatal high exposures to PM2.5, O3, combustion-derived iron-rich nanoparticles, metals, polycyclic aromatic hydrocarbons, and endotoxins...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28523554/alzheimer-s-disease-and-histone-code-alterations
#17
Pritika Narayan, Mike Dragunow
Substantial progress has been made in identifying Alzheimer's disease (AD) risk-associated variants using genome-wide association studies (GWAS). The majority of these risk variants reside in noncoding regions of the genome making their functional evaluation difficult; however, they also infer the presence of unconventional regulatory regions that may reside at these locations. We know from these studies that rare familial cases of AD account for less than 5% of all AD cases and autosomal dominant mutations in APP, PSEN1 and PSEN2 account for less than 10% of the genetic basis of these familial cases [1]...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28495939/apoe-e4-is-associated-with-gray-matter-loss-in-the-posterior-cingulate-cortex-in-healthy-elderly-controls-subsequently-developing-subtle-cognitive-decline
#18
S Haller, M-L Montandon, C Rodriguez, M Ackermann, F R Herrmann, P Giannakopoulos
BACKGROUND AND PURPOSE: The presence of apolipoprotein E4 (APOE*E4) is the strongest currently known genetic risk factor for Alzheimer disease and is associated with brain gray matter loss, notably in areas involved in Alzheimer disease pathology. Our objective was to assess the effect of APOE*E4 on brain structures in healthy elderly controls who subsequently developed subtle cognitive decline. MATERIALS AND METHODS: This prospective study included 382 community-dwelling elderly controls...
May 11, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28492093/higher-prevalence-of-cerebral-white-matter-hyperintensities-in-homozygous-apoe-%C3%A9-4-allele-carriers-aged-45-75-results-from-the-alfa-study
#19
Santiago Rojas, Anna Brugulat-Serrat, Nuria Bargalló, Carolina Minguillón, Alan Tucholka, Carles Falcon, Andreia Carvalho, Sebastian Morán, Manel Esteller, Nina Gramunt, Karine Fauria, Jordi Camí, José L Molinuevo, Juan D Gispert
Cerebral white matter hyperintensities are believed the consequence of small vessel disease and are associated with risk and progression of Alzheimer's disease. The ɛ4 allele of the APOE gene is the major factor accountable for Alzheimer's disease heritability. However, the relationship between white matter hyperintensities and APOE genotype in healthy subjects remains controversial. We investigated the association between APOE-ɛ4 and vascular risk factors with white matter hyperintensities, and explored their interactions, in a cohort of cognitively healthy adults (45-75 years)...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28482100/apoe-genotype-and-non-respiratory-sleep-parameters-in-cognitively-intact-older-adults
#20
Adam P Spira, Yang An, Yu Peng, Mark N Wu, Eleanor M Simonsick, Luigi Ferrucci, Susan M Resnick
Study Objectives: The apolipoprotein E (APOE) Ɛ4 allele increases Alzheimer's disease (AD) risk and has been linked to a greater risk of sleep-disordered breathing. We investigated the association of APOE genotype with non-respiratory sleep parameters. Methods: We studied 1,264 cognitively normal participants in the Baltimore Longitudinal Study of Aging (mean = 57.5±16.1 years, range 19.9-92.0, 48.2% women, 19.8% African American) with APOE genotyping and self-reported sleep duration (≥9, 7 or 8, ≤6 hours), difficulty falling/staying asleep, and napping...
May 6, 2017: Sleep
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