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Apo E4

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https://www.readbyqxmd.com/read/28106546/a-common-variant-of-il-6r-is-associated-with-elevated-il-6-pathway-activity-in-alzheimer-s-disease-brains
#1
Patrick C G Haddick, Jessica L Larson, Nisha Rathore, Tushar R Bhangale, Qui T Phung, Karpagam Srinivasan, David V Hansen, Jennie R Lill, Margaret A Pericak-Vance, Jonathan Haines, Lindsay A Farrer, John S Kauwe, Gerard D Schellenberg, Carlos Cruchaga, Alison M Goate, Timothy W Behrens, Ryan J Watts, Robert R Graham, Joshua S Kaminker, Marcel van der Brug
The common p.D358A variant (rs2228145) in IL-6R is associated with risk for multiple diseases and with increased levels of soluble IL-6R in the periphery and central nervous system (CNS). Here, we show that the p.D358A allele leads to increased proteolysis of membrane bound IL-6R and demonstrate that IL-6R peptides with A358 are more susceptible to cleavage by ADAM10 and ADAM17. IL-6 responsive genes were identified in primary astrocytes and microglia and an IL-6 gene signature was increased in the CNS of late onset Alzheimer's disease subjects in an IL6R allele dependent manner...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28103200/depressive-symptoms-influence-global-cognitive-impairment-indirectly-by-reducing-memory-and-executive-function-in-patients-with-mild-cognitive-impairment
#2
Chathuri Yatawara, Levinia Lim, Russell Chander, Juan Zhou, Nagaendran Kandiah
BACKGROUND: Depressive symptoms negatively influence global cognition in the elderly; however, the mechanism of this effect remains unclear. OBJECTIVE: To investigate whether depressive symptoms influence global cognitive function in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) by impeding specific neuropsychological abilities and under what conditions this effect might occur. METHOD: A sample of 259 participants (104 cognitively normal elderly controls, 66 patients with MCI and 89 patients with mild AD) underwent a comprehensive neuropsychological assessment...
December 2016: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28099631/associations-of-cerebrovascular-metabolism-genotypes-with-neuropsychiatric-symptoms-and-age-at-onset-of-alzheimer-s-disease-dementia
#3
Fabricio F de Oliveira, Elizabeth S Chen, Marilia C Smith, Paulo H Bertolucci
Objective: To study associations of cerebrovascular metabolism genotypes and haplotypes with age at Alzheimer's disease dementia (AD) onset and with neuropsychiatric symptoms according to each dementia stage. Methods: Consecutive outpatients with late-onset AD were assessed for age at dementia onset and Neuropsychiatric Inventory scores according to Clinical Dementia Rating scores, apolipoprotein E gene (APOE) haplotypes, angiotensin-converting enzyme gene (ACE) variants rs1800764 and rs4291, low-density lipoprotein cholesterol receptor gene (LDLR) variants rs11669576 and rs5930, cholesteryl ester transfer protein gene (CETP) variants I422V and TaqIB, and liver X receptor beta gene (NR1H2) polymorphism rs2695121...
January 12, 2017: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/28096372/helical-structure-stability-and-dynamics-in-human-apolipoprotein-e3-and-e4-by-hydrogen-exchange-and-mass-spectrometry
#4
Palaniappan S Chetty, Leland Mayne, Sissel Lund-Katz, S Walter Englander, Michael C Phillips
Apolipoprotein E (apoE) plays a critical role in cholesterol transport in both peripheral circulation and brain. Human apoE is a polymorphic 299-residue protein in which the less common E4 isoform differs from the major E3 isoform only by a C112R substitution. ApoE4 interacts with lipoprotein particles and with the amyloid-β peptide, and it is associated with increased incidence of cardiovascular and Alzheimer's disease. To understand the structural basis for the differences between apoE3 and E4 functionality, we used hydrogen-deuterium exchange coupled with a fragment separation method and mass spectrometric analysis to compare their secondary structures at near amino acid resolution...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28072416/preclinical-amyloid-pathology-biomarker-positivity-effects-on-tau-pathology-and-neurodegeneration
#5
K Höglund, S Kern, A Zettergren, A Börjesson-Hansson, H Zetterberg, I Skoog, K Blennow
Brain autopsy and biomarker studies indicate that the pathology of Alzheimer's disease (AD) is initiated at least 10-20 years before clinical symptoms. This provides a window of opportunity to initiate preventive treatment. However, this emphasizes the necessity for biomarkers that identify individuals at risk for developing AD later in life. In this cross-sectional study, originating from three epidemiologic studies in Sweden (n=1428), the objective was to examine whether amyloid pathology, as determined by low cerebrospinal fluid (CSF) concentration of the 42 amino acid form of β-amyloid (Aβ42), is associated with biomarker evidence of other pathological changes in cognitively healthy elderly...
January 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28059047/the-elusive-nature-of-apoe-%C3%AE%C2%B54-in-mid-adulthood-understanding-the-cognitive-profile
#6
Claire Lancaster, Naji Tabet, Jennifer Rusted
OBJECTIVES: The apolipoprotein E (APOE) ε4 allele is an established risk factor for dementia, yet this genetic variant is associated with a mixed cognitive profile across the lifespan. This study undertakes both a systematic and meta-analytic review of research investigating APOE-related differences in cognition in mid-adulthood, when detrimental effects of the allele may first be detectable. METHODS: Thirty-six papers investigating the behavioral effects of APOE ε4 in mid-adulthood (defined as a mean sample age between 35 and 60 years) were reviewed...
January 6, 2017: Journal of the International Neuropsychological Society: JINS
https://www.readbyqxmd.com/read/28057414/apoe-apoe-receptors-and-the-synapse-in-alzheimer-s-disease
#7
REVIEW
Courtney Lane-Donovan, Joachim Herz
As the population ages, neurodegenerative diseases such as Alzheimer's disease (AD) are becoming a significant burden on patients, their families, and health-care systems. Neurodegenerative processes may start up to 15 years before outward signs and symptoms of AD, as evidenced by data from AD patients and mouse models. A major genetic risk factor for late-onset AD is the ɛ4 isoform of apolipoprotein E (ApoE4), which is present in almost 20% of the population. In this review we discuss the contribution of ApoE receptor signaling to the function of each component of the tripartite synapse - the axon terminal, the postsynaptic dendritic spine, and the astrocyte - and examine how these systems fail in the context of ApoE4 and AD...
January 2, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28052883/association-of-dietary-cholesterol-and-egg-intakes-with-the-risk-of-incident-dementia-or-alzheimer-disease-the-kuopio-ischaemic-heart-disease-risk-factor-study
#8
Maija Pt Ylilauri, Sari Voutilainen, Eija Lönnroos, Jaakko Mursu, Heli Ek Virtanen, Timo T Koskinen, Jukka T Salonen, Tomi-Pekka Tuomainen, Jyrki K Virtanen
BACKGROUND: There is little information about the associations of intakes of cholesterol and eggs, a major source of dietary cholesterol, with the risk of cognitive decline in general populations or in carriers of apolipoprotein E ɛ4 (APO-E4), a major risk factor for dementia. OBJECTIVE: We investigated the associations of cholesterol and egg intakes with incident dementia, Alzheimer disease (AD), and cognitive performance in middle-aged and older men from Eastern Finland...
January 4, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28035934/the-association-between-plasma-ceramides-and-sphingomyelins-and-risk-of-alzheimer-s-disease-differs-by-sex-and-apoe-in-the-baltimore-longitudinal-study-of-aging
#9
Michelle M Mielke, Norman J Haughey, Dingfen Han, Yang An, Veera Venkata Ratnam Bandaru, Constantine G Lyketsos, Luigi Ferrucci, Susan M Resnick
BACKGROUND: Cellular and animal studies demonstrated relationships between sphingolipid metabolism and Alzheimer's disease (AD) pathology. High blood ceramide levels have been shown to predict cognitive impairment and AD, but these studies had small sample sizes and did not assess differences in risk by sex or APOE genotype. OBJECTIVE: To determine whether plasma ceramides and sphingomyelins were associated with risk of AD, and whether the association varied by sex and APOE genotype...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28035926/pleiotropic-effect-of-human-apoe4-on-cerebral-ceramide-and-saturated-fatty-acid-levels
#10
Sandra den Hoedt, Carola I F Janssen, Guiseppe Astarita, Daniele Piomelli, Frank P J Leijten, Simone M Crivelli, Adrie J M Verhoeven, Helga E de Vries, Jochen Walter, Pilar Martinez-Martinez, Eric J G Sijbrands, Amanda J Kiliaan, Monique T Mulder
BACKGROUND: Apolipoprotein E (ApoE) is known for its role in lipid trafficking and the ɛ4 allele is a risk factor for late onset Alzheimer's disease (AD). Recently, aberrant ceramide and fatty acid (FA) levels have been implicated in AD. OBJECTIVE: To determine the specific effects of human ApoE4 (hE4) on cerebral ceramide and FA content during chow or a high fat/high cholesterol (HFHC) diet. METHODS: Cerebral ceramide and FA profiles were determined by LC-MSMS in 15-month-old female wild-type (WT), ApoE-knockout (E0), and hE4-knockin mice fed chow or a HFHC diet for 3 months...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28035917/apolipoprotein-e4-elicits-lysosomal-cathepsin-d-release-decreased-thioredoxin-1-levels-and-apoptosis
#11
Torbjörn Persson, Francesca Lattanzio, Javier Calvo-Garrido, Roberto Rimondini, Marta Rubio-Rodrigo, Erik Sundström, Silvia Maioli, Anna Sandebring-Matton, Ángel Cedazo-Mínguez
The major genetic risk factor for Alzheimer's disease (AD), apolipoprotein E4 (ApoE4), has been suggested to have detrimental effects on neurons, including direct toxicity via apoptosis. Thioredoxin-1 (Trx1) is an endogenous antioxidant protein important for redox regulation and participates in the regulation of apoptosis through the inhibition of apoptosis signal-regulating kinase-1 (Ask-1). In this study, we have investigated the effects of ApoE on Trx1 in the brain. Our results showed that the protein levels of Trx1 were reduced in the hippocampus of ApoE4 targeted replacement (TR) mice compared to ApoE3 TR mice...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28025282/memory-resilience-to-alzheimer-s-genetic-risk-sex-effects-in-predictor-profiles
#12
Kirstie L McDermott, G Peggy McFall, Shea J Andrews, Kaarin J Anstey, Roger A Dixon
OBJECTIVES: Apolipoprotein E (APOE) ɛ4 and Clusterin (CLU) C alleles are risk factors for Alzheimer's disease (AD) and episodic memory (EM) decline. Memory resilience occurs when genetically at-risk adults perform at high and sustained levels. We investigated whether (a) memory resilience to AD genetic risk is predicted by biological and other risk markers and (b) the prediction profiles vary by sex and AD risk variant. METHOD: Using a longitudinal sample of nondemented adults (n = 642, aged 53-95) we focused on memory resilience (over 9 years) to 2 AD risk variants (APOE, CLU)...
December 26, 2016: Journals of Gerontology. Series B, Psychological Sciences and Social Sciences
https://www.readbyqxmd.com/read/28003161/apolipoprotein-e4-causes-early-olfactory-network-abnormalities-and-short-term-olfactory-memory-impairments
#13
Katherine Y Peng, Paul M Mathews, Efrat Levy, Donald A Wilson
While apolipoprotein (Apo) E4 is linked to increased incidence of Alzheimer's disease (AD), there is growing evidence that it plays a role in functional brain irregularities that are independent of AD pathology. However, ApoE4-driven functional differences within olfactory processing regions have yet to be examined. Utilizing knock-in mice humanized to ApoE4 versus the more common ApoE3, we examined a simple olfactory perceptual memory that relies on the transfer of information from the olfactory bulb (OB) to the piriform cortex (PCX), the primary cortical region involved in higher order olfaction...
December 18, 2016: Neuroscience
https://www.readbyqxmd.com/read/27977609/serum-apolipoprotein-e-concentration-and-polymorphism-influence-serum-lipid-levels-in-chinese-shandong-han-population
#14
ShuYi Han, YiHui Xu, MeiHua Gao, YunShan Wang, Jun Wang, YanYan Liu, Min Wang, XiaoQian Zhang
Apolipoprotein E (ApoE), which has been shown to influence serum lipid parameters, can bind to multiple types of lipids and plays an important role in the metabolism and homeostasis of lipids and lipoproteins. A previous study showed that ApoE concentration significantly affects serum lipid levels independently of ApoE polymorphism. The serum lipid levels were also closely correlated with dietary habits, and Shandong cuisine is famous for its high salt and oil contents, which widely differ among the different areas in China...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27935250/apolipoprotein-e-epsilon-genotype-has-a-greater-impact-on-apob-48-than-apob-100-responses-to-dietary-fat-manipulation-insights-from-the-satgen%C3%AE%C2%B5-study
#15
Kim G Jackson, Stacey Lockyer, Andrew L Carvalho-Wells, Christine M Williams, Anne M Minihane, Julie A Lovegrove
SCOPE: To determine the contribution of intestinally and liver-derived lipoproteins to the postprandial plasma triacylglycerol (TAG) response in APOE3/E3 and E3/E4 individuals following chronic dietary fat manipulation. METHODS AND RESULTS: In sequential order, participants (n = 12 E3/E3, n = 11 E3/E4) followed low fat (LF); high-fat, high-saturated fat (HSF); and HSF with 3.45 g/day docosahexaenoic acid (HSF-DHA) diets, each for 8 weeks. After each dietary period, an acute test meal with a macronutrient profile representative of the dietary intervention was consumed...
December 9, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27932854/predictors-of-ageing-related-decline-across-multiple-cognitive-functions
#16
Stuart J Ritchie, Elliot M Tucker-Drob, Simon R Cox, Janie Corley, Dominika Dykiert, Paul Redmond, Alison Pattie, Adele M Taylor, Ruth Sibbett, John M Starr, Ian J Deary
It is critical to discover why some people's cognitive abilities age better than others'. We applied multivariate growth curve models to data from a narrow-age cohort measured on a multi-domain IQ measure at age 11 years and a comprehensive battery of thirteen measures of visuospatial, memory, crystallized, and processing speed abilities at ages 70, 73, and 76 years (n = 1091 at age 70). We found that 48% of the variance in change in performance on the thirteen cognitive measures was shared across all measures, an additional 26% was specific to the four ability domains, and 26% was test-specific...
November 2016: Intelligence
https://www.readbyqxmd.com/read/27911306/cortical-thickness-and-microstructural-white-matter-changes-detect-amnestic-mild-cognitive-impairment
#17
Zan Wang, Zhengjia Dai, Hao Shu, Duan Liu, Qihao Guo, Yong He, Zhijun Zhang
Both the apolipoprotein E (APOE) ɛ4 allele and amnestic mild cognitive impairment (aMCI) are considered to be risk factors for Alzheimer's disease (AD). The primary aim of this study was to determine whether the aMCI-related abnormality in gray matter (GM) cortical thickness and white matter (WM) tracts integrity would be modified by the APOE genotype. A total of 146 older adults, including 64 aMCI patients (28 ɛ4 carriers and 36 non-carriers) and 82 healthy controls (39 ɛ4 carriers and 43 non-carriers), underwent a standardized clinical interview, neuropsychological battery assessment, and multi-modal brain magnetic resonance imaging scans...
November 29, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911292/physical-exercise-moderates-the%C3%A2-relationship-of-apolipoprotein-e-apoe-%C3%A2-genotype-and-dementia-risk-a%C3%A2-population-based-study
#18
Barbara Fenesi, Hanna Fang, Ana Kovacevic, Mark Oremus, Parminder Raina, Jennifer J Heisz
Genetics and lifestyle independently determine dementia risk, but the interaction is unclear. We assessed the interactive relationship of apolipoprotein E (APOE) genotype and physical exercise on dementia risk over a 5-year period in 1,646 older adults from the Canadian Study of Health and Aging who were dementia-free at baseline. Physical exercise moderated the relationship between genotype and dementia (p < 0.01). Specifically, for APOE ɛ4 non-carriers, the odds of developing dementia were higher in non-exercisers than exercisers (OR = 1...
November 29, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911290/rare-genetic-variant-in-sorl1-may-increase-penetrance-of-alzheimer-s-disease-in-a-family-with-several-generations-of-apoe-%C3%A9-4-homozygosity
#19
Eva Louwersheimer, Petra E Cohn-Hokke, Yolande A L Pijnenburg, Marjan M Weiss, Erik A Sistermans, Annemieke J Rozemuller, Marc Hulsman, John C van Swieten, Cock M van Duijn, Frederik Barkhof, Teddy Koene, Philip Scheltens, Wiesje M Van der Flier, Henne Holstege
BACKGROUND: The major genetic risk factor for late onset Alzheimer's disease (AD) is the APOE-ɛ4 allele. However, APOE-ɛ4 homozygosity is not fully penetrant, suggesting co-occurrence of additional genetic variants. OBJECTIVE: To identify genetic factors that, next to APOE-ɛ4 homozygosity, contribute to the development of AD. METHODS: We identified a family with nine AD patients spanning four generations, with an inheritance pattern suggestive of autosomal dominant AD, with no variants in PSEN1, PSEN2, or APP...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27895004/predictors-of-vascular-cognitive-impairment-poststroke-in-a-middle-eastern-bahrain-cohort-a-proposed-case-control-comparison
#20
Claire Donnellan, Mona Al Banna, Noor Redha, Adel Al Jishi, Isa Al Sharoqi, Safa Taha, Moiz Bakhiet, Fatema Abdulla, Patrick Walsh
BACKGROUND: Poststroke dementia and cognitive impairment are associated with poor long-term outcomes after stroke. The contribution of genetic factors such as the presence of apolipoprotein (ApoE) ɛ4 allele and its association with cognitive impairment poststroke remains inconclusive, particularly in Middle Eastern regions. OBJECTIVE: The aim of this study is to examine all correlates and potential predictors of cognitive impairment including self-awareness and regulation deficits in stroke patients and compare these functions with healthy older adults from a Middle Eastern population...
November 28, 2016: JMIR Research Protocols
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