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https://www.readbyqxmd.com/read/27911294/deleterious-effect-of-butyrylcholinesterase-k-variant-in-donepezil-treatment-of-mild-cognitive-impairment
#1
Sophie Sokolow, Xiaohui Li, Lucia Chen, Kent D Taylor, Jerome I Rotter, Robert A Rissman, Paul S Aisen, Liana G Apostolova
BACKGROUND: Donepezil is an acetylcholinesterase inhibitor frequently prescribed for the treatment of mild cognitive impairment (MCI) though not approved by the Food and Drug Administration for this indication. In Alzheimer's disease, butyrylcholinesterase (BChE) activity increases with disease progression and may replace acetylcholinesterase function. The most frequent polymorphism of BChE is the K-variant, which is associated with lower acetylcholine-hydrolyzing activity. BChE-K polymorphism has been studied in Alzheimer's disease progression and donepezil therapy, and has led to contradictory results...
November 29, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27896962/adaptive-testing-of-snp-brain-functional-connectivity-association-via-a-modular-network-analysis
#2
Chen Gao, Junghi Kim, Wei Pan
Due to its high dimensionality and high noise levels, analysis of a large brain functional network may not be powerful and easy to interpret; instead, decomposition of a large network into smaller subcomponents called modules may be more promising as suggested by some empirical evidence. For example, alteration of brain modularity is observed in patients suffering from various types of brain malfunctions. Although several methods exist for estimating brain functional networks, such as the sample correlation matrix or graphical lasso for a sparse precision matrix, it is still difficult to extract modules from such network estimates...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27895108/the-effect-of-dietary-fish-oil-on-weight-gain-and-insulin-sensitivity-is-dependent-on-apoe-genotype-in-humanized-targeted-replacement-mice
#3
Kenna E Slim, David Vauzour, Noemi Tejera, Peter J Voshol, Aedin Cassidy, Anne Marie Minihane
We investigated the independent and interactive impact of the common APOE genotype and marine n-3 polyunsaturated fatty acids (PUFA) on the development of obesity and associated cardiometabolic dysfunction in a murine model. Human APOE3 and APOE4 targeted replacement mice were fed either a high-fat control diet (HFD) or a HFD supplemented with 3% n-3 PUFA from fish oil (HFD + FO) for 8 wk. We established the impact of intervention on food intake, bodyweight, and visceral adipose tissue (VAT) mass; plasma, lipids (cholesterol and triglycerides), liver enzymes, and adipokines; glucose and insulin during an intraperitoneal glucose tolerance test; and Glut4 and ApoE expression in VAT...
November 28, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27855547/traumatic-brain-injury-history-is-associated-with-earlier-age-of-onset-of-alzheimer-disease
#4
Christian LoBue, Hannah Wadsworth, Kristin Wilmoth, Matthew Clem, John Hart, Kyle B Womack, Nyaz Didehbani, Laura H Lacritz, Heidi C Rossetti, C Munro Cullum
OBJECTIVE: This study examined whether a history of traumatic brain injury (TBI) is associated with earlier onset of Alzheimer disease (AD), independent of apolipoprotein ε4 status (Apoe4) and gender. METHOD: Participants with a clinical diagnosis of AD (n = 7625) were obtained from the National Alzheimer's Coordinating Center Uniform Data Set, and categorized based on self-reported lifetime TBI with loss of consciousness (LOC) (TBI+ vs. TBI-) and presence of Apoe4...
November 18, 2016: Clinical Neuropsychologist
https://www.readbyqxmd.com/read/27830118/variable-phenotypic-expression-of-nonsense-mutation-p-thr5-in-the-apoe-gene
#5
Trond P Leren, Thea Bismo Strøm, Knut Erik Berge
Subjects with hypercholesterolemia who do not carry a mutation in the low density lipoprotein receptor gene, in the apolipoprotein B gene or in the proprotein convertase subtilisin/kexin type 9 gene, could possible carry a mutation in the apolipoprotein E (APOE) gene. DNA from 844 unrelated hypercholesterolemic subjects who did not carry a mutation in any of the three above mentioned genes, was subjected to DNA sequencing of the APOE gene. Two subjects were found to be heterozygous for mutation p.Thr5*. This mutation which generates a stop codon in the signal peptide, is assumed to prevent the synthesis of APOE...
December 2016: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/27824936/differential-effects-of-apoe4-and-activation-of-abca1-on-brain-and-plasma-lipoproteins
#6
Anat Boehm-Cagan, Roni Bar, Dror Harats, Aviv Shaish, Hana Levkovitz, John K Bielicki, Jan O Johansson, Daniel M Michaelson
Apolipoprotein E4 (apoE4), the leading genetic risk factor for Alzheimer's disease (AD), is less lipidated compared to the most common and AD-benign allele, apoE3. We have recently shown that i.p. injections of the ATP-binding cassette A1 (ABCA1) agonist peptide CS-6253 to apoE mice reverse the hypolipidation of apoE4 and the associated brain pathology and behavioral deficits. While in the brain apoE is the main cholesterol transporter, in the periphery apoE and apoA-I both serve as the major cholesterol transporters...
2016: PloS One
https://www.readbyqxmd.com/read/27814298/micrornas-in-human-cerebrospinal-fluid-as-biomarkers-for-alzheimer-s-disease
#7
Theresa A Lusardi, Jay I Phillips, Jack T Wiedrick, Christina A Harrington, Babett Lind, Jodi A Lapidus, Joseph F Quinn, Julie A Saugstad
BACKGROUND: Currently available biomarkers of Alzheimer's disease (AD) include cerebrospinal fluid (CSF) protein analysis and amyloid PET imaging, each of which has limitations. The discovery of extracellular microRNAs (miRNAs) in CSF raises the possibility that miRNA may serve as novel biomarkers of AD. OBJECTIVE: Investigate miRNAs in CSF obtained from living donors as biomarkers for AD. METHODS: We profiled miRNAs in CSF from 50 AD patients and 49 controls using TaqMan® arrays...
November 3, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27805616/a-high-throughput-multiplexed-and-targeted-proteomic-csf-assay-to-quantify-neurodegenerative-biomarkers-and-apolipoprotein-e-isoforms-status
#8
Wendy E Heywood, Anna Baud, Emily Bliss, Ernestas Sirka, Jonathan M Schott, Henrik Zetterberg, Daniela Galimberti, Neil J Sebire, Kevin Mills
Many neurodegenerative diseases are still lacking effective treatments. Reliable biomarkers for identifying and classifying these diseases will be important in the development of future novel therapies. Often potential new biomarkers do not make it into the clinic due to limitations in their development and high costs. However, targeted proteomics using Multiple Reaction Monitoring Liquid Chromatography-tandem/Mass Spectrometry (MRM LC-MS/MS), specifically using triple quadrupole mass spectrometers, is one method that can be used to rapidly evaluate and validate biomarkers for clinical translation into diagnostic laboratories...
October 20, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27802227/effects-of-alzheimer-s-disease-associated-risk-loci-on-amyloid-%C3%AE-accumulation-in-the-brain-of-idiopathic-normal-pressure-hydrocephalus-patients
#9
Tiina Laiterä, Jussi Paananen, Seppo Helisalmi, Timo Sarajärvi, Joel Huovinen, Marjo Laitinen, Tuomas Rauramaa, Irina Alafuzoff, Anne M Remes, Hilkka Soininen, Annakaisa Haapasalo, Juha E Jääskeläinen, Ville Leinonen, Mikko Hiltunen
BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a dementing condition featuring characteristic symptoms, ventriculomegaly, and normal or slightly elevated cerebrospinal fluid pressure. In Alzheimer's disease (AD) patients, diffuse aggregates of amyloid-β (Aβ) and neurofibrillary hyperphosphorylated tau are detected in the neocortex of the brain, while similar accumulation of Aβ is also detected in iNPH. Recent genome-wide association studies have identified several novel risk loci for AD, potentially affecting Aβ-related cellular processes...
October 11, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27793990/human-central-nervous-system-cns-apoe-isoforms-are-increased-by-age-differentially-altered-by-amyloidosis-and-relative-amounts-reversed-in-the-cns-compared-to-plasma
#10
Alaina T Baker-Nigh, Kwasi G Mawuenyega, James G Bollinger, Vitaliy Ovod, Tom Kasten, Erin E Franklin, Fan Liao, Hong Jiang, David Holtzman, Nigel J Cairns, John C Morris, Randall J Bateman
The risk of Alzheimers Disease (AD) is highly dependent on apolipoprotein-E (ApoE) genotype. The reasons for ApoE isoform-selective risk are uncertain, however, both the amounts and structure of human ApoE isoforms have been hypothesized to lead to amyloidosis increasing risk for AD. In order to address the hypothesis that amounts of ApoE isoforms are different in the human CNS, we developed a novel isoform-specific method to accurately quantify ApoE isoforms in clinically relevant samples. The method utilizes an antibody-free enrichment step and isotope labelled physiologically-relevant lipoprotein particle standards produced by immortalized astrocytes...
October 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27789405/episomal-plasmid-based-generation-of-an-ipsc-line-from-a-79-year-old-individual-carrying-the-apoe4-4-genotype-i11001
#11
Shadaan Zulfiqar, Barbara Fritz, Katja Nieweg
In this study, lymphoblastoid cells derived from a 79-year old individual with a history of progressive presenile dementia, were used to generate iPS cells, employing episomal plasmids expressing OCT4, SOX2, KLF4, LIN28, L-MYC and a p53 shRNA. The individual was homozygous for the APOE4 allele. The resulting iPS cells had a normal karyotype, retained the APOE4/4 genotype, expressed pluripotency markers, were free of genomically integrated plasmids, and could be differentiated into cell type representatives from the three germ layers in vitro...
September 23, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789402/episomal-plasmid-based-generation-of-an-ipsc-line-from-an-83-year-old-individual-carrying-the-apoe4-4-genotype-i10984
#12
Shadaan Zulfiqar, Barbara Fritz, Katja Nieweg
In this study, lymphoblastoid cells derived from a 83-year old individual with a 15year history of progressive presenile dementia, were used to generate iPS cells, employing episomal plasmids expressing OCT4, SOX2, LIN28, L-MYC and a p53 shRNA. The individual was homozygous for the APOE4 allele. The resulting iPS cells had a normal karyotype, retained the APOE4/4 genotype, expressed pluripotency markers, were free of genomically integrated plasmids, and could be differentiated into cell type representatives from the three germ layers in vitro...
September 24, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27788676/epidermal-growth-factor-prevents-apoe4-and-amyloid-beta-induced-cognitive-and-cerebrovascular-deficits-in-female-mice
#13
Riya Thomas, Paulina Zuchowska, Alan W J Morris, Felecia M Marottoli, Sangeeta Sunny, Ryan Deaton, Peter H Gann, Leon M Tai
Cerebrovascular (CV) dysfunction is emerging as a critical component of Alzheimer's disease (AD), including altered CV coverage. Angiogenic growth factors (AGFs) are key for controlling CV coverage, especially during disease pathology. Therefore, evaluating the effects of AGFs in vivo can provide important information on the role of CV coverage in AD. We recently demonstrated that epidermal growth factor (EGF) prevents amyloid-beta (Aβ)-induced damage to brain endothelial cells in vitro. Here, our goal was to assess the protective effects of EGF on cognition, CV coverage and Aβ levels using an AD-Tg model that incorporates CV relevant AD risk factors...
October 27, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27767986/serum-shbg-levels-are-not-associated-with-longitudinal-cognitive-decline-in-mild-cognitive-impairment
#14
Katherine Amy Lin, Colin Rundel, P Murali Doraiswamy
BACKGROUND: Prior studies have noted gender differences in cognition, imaging, and pathological markers in mild cognitive impairment (MCI) subjects. Sex hormone-binding globulin (SHBG), a major controlling factor in the proportion of bioavailable versus bound testosterone and estrogen, has been proposed to contribute to links between hormones and dementia, but has not yet been investigated fully in a prospective biomarker trial. OBJECTIVE: This study examined whether, among subjects with MCI, SHBG levels predict future rate of cognitive decline...
October 20, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27733827/a-triple-network-connectivity-study-of-large-scale-brain-systems-in-cognitively-normal-apoe4-carriers
#15
Xia Wu, Qing Li, Xinyu Yu, Kewei Chen, Adam S Fleisher, Xiaojuan Guo, Jiacai Zhang, Eric M Reiman, Li Yao, Rui Li
The triple network model, consisting of the central executive network (CEN), salience network (SN) and default mode network (DMN), has been recently employed to understand dysfunction in core networks across various disorders. Here we used the triple network model to investigate the large-scale brain networks in cognitively normal apolipoprotein e4 (APOE4) carriers who are at risk of Alzheimer's disease (AD). To explore the functional connectivity for each of the three networks and the effective connectivity among them, we evaluated 17 cognitively normal individuals with a family history of AD and at least one copy of the APOE4 allele and compared the findings to those of 12 individuals who did not carry the APOE4 gene or have a family history of AD, using independent component analysis (ICA) and Bayesian network (BN) approach...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27717947/-predictive-value-of-apolipoproteine-e-genotypes
#16
Joanna Martenka, Krystyna Soszyńska
Apolipoprotein E is a transport protein, which by binding to lipids forms a lipoprotein particle. It is responsible for transport and redistribution of lipids between cells and tissues. Apolipoprotein E circulates in blood mainly as a component of VLDL (very low density lipoproteins) HDL (high density lipoproteins) chylomicrons and chylomicron remnants. It assists in the flow of cholesterol from peripheral cells to extracellular space. Apolipoprotein E is one of the most studied apolipoproteins. There are three isoforms of this protein: E2, E3 and E4...
2016: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/27709233/vitamin-c-supplementation-apoe4-genotype-and-cognitive-functioning-in-a-rural-dwelling-cohort
#17
K Chaudhari, N Sumien, L Johnson, D D'Agostino, M Edwards, R J Paxton, J R Hall, S O'Bryant
OBJECTIVE: Apolipoprotein E4 (APOE4) genotype has been implicated as a moderating factor in cognitive function studies. Although prior studies have suggested that vitamin C is associated with better cognitive function in elders, link between the two has been mixed. Limited data exist as to whether the APOE4 genotype influences these associations. Therefore, this study sought to determine whether the association between vitamin C and cognition in a rural community dwelling cohort differs by the APOE4 genotype...
2016: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/27707979/apoe-sensitive-cholinergic-sprouting-compensates-for-hippocampal-dysfunctions-due-to-reduced-entorhinal-input
#18
Jean-Bastien Bott, Céline Héraud, Brigitte Cosquer, Karine Herbeaux, Julien Aubert, Maxime Sartori, Romain Goutagny, Chantal Mathis
: Brain mechanisms compensating for cerebral lesions may mitigate the progression of chronic neurodegenerative disorders such as Alzheimer's disease (AD). Mild cognitive impairment (MCI), which often precedes AD, is characterized by neuronal loss in the entorhinal cortex (EC). This loss leads to a hippocampal disconnection syndrome that drives clinical progression. The concomitant sprouting of cholinergic terminals in the hippocampus has been proposed to compensate for reduced EC glutamatergic input...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27699079/education-and-genetic-risk-modulate-hippocampal-structure-in-alzheimer-s-disease
#19
Johanna Baumgaertel, Robert Haussmann, Antonia Gruschwitz, Annett Werner, Antje Osterrath, Jan Lange, Katharina L Donix, Jennifer Linn, Markus Donix
Genetic and environmental protective factors and risks modulate brain structure and function in neurodegenerative diseases and their preclinical stages. We wanted to investigate whether the years of formal education, a proxy measure for cognitive reserve, would influence hippocampal structure in Alzheimer's disease patients, and whether apolipoprotein Eε4 (APOE4) carrier status and a first-degree family history of the disease would change a possible association. Fifty-eight Alzheimer's disease patients underwent 3T magnetic resonance imaging...
October 2016: Aging and Disease
https://www.readbyqxmd.com/read/27683909/genetic-restoration-of-plasma-apoe-improves-cognition-and-partially-restores-synaptic-defects-in-apoe-deficient-mice
#20
Courtney Lane-Donovan, Wen Mai Wong, Murat S Durakoglugil, Catherine R Wasser, Shan Jiang, Xunde Xian, Joachim Herz
UNLABELLED: Alzheimer's disease (AD) is the most common form of dementia in individuals over the age of 65 years. The most prevalent genetic risk factor for AD is the ε4 allele of apolipoprotein E (ApoE4), and novel AD treatments that target ApoE are being considered. One unresolved question in ApoE biology is whether ApoE is necessary for healthy brain function. ApoE knock-out (KO) mice have synaptic loss and cognitive dysfunction; however, these findings are complicated by the fact that ApoE knock-out mice have highly elevated plasma lipid levels, which may independently affect brain function...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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