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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
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
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
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
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
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
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
Francesca Zimetti, Paolo Caffarra, Nicoletta Ronda, Elda Favari, Maria Pia Adorni, Ilaria Zanotti, Franco Bernini, Federica Barocco, Marco Spallazzi, Daniela Galimberti, Chiara Ricci, Massimiliano Ruscica, Alberto Corsini, Nicola Ferri
BACKGROUND: Alzheimer's disease (AD) has been associated with dysregulation of brain cholesterol trafficking and abnormal production of apolipoprotein E isoform 4 (apoE4). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein present in serum and cerebrospinal fluid (CSF) degrading the low-density lipoprotein receptor (LDLr) and other apoE-binding receptors involved in neuron cholesterol uptake. The role of PCSK9 in AD is controversial. OBJECTIVE: We compared PCSK9 levels in CSF of AD patients and non-AD controls and looked at correlations with CSF total apoE and apoE4...
September 20, 2016: Journal of Alzheimer's Disease: JAD
M V Spampinato, B R Langdon, K E Patrick, R O Parker, H Collins, E Pravata'
INTRODUCTION: This study aimed to examine the relationship between gender, apolipoprotein E (APOE) genotype, and mesial temporal atrophy in mild cognitive impairment (MCI) with and without progression to Alzheimer's disease (AD). METHODS: We evaluated 236 MCI patients with (n = 121) and without (n = 115) AD progression. Longitudinal MRI-based hippocampal volumes (HV) and entorhinal cortex (ERC) thickness were obtained. The Clinical Dementia Rating Sum of Boxes (CDR-SB) score was used to assess disease severity...
September 2, 2016: Neuroradiology
Annie M Racine, Lindsay R Clark, Sara E Berman, Rebecca L Koscik, Kimberly D Mueller, Derek Norton, Christopher R Nicholas, Kaj Blennow, Henrik Zetterberg, Bruno Jedynak, Murat Bilgel, Cynthia M Carlsson, Bradley T Christian, Sanjay Asthana, Sterling C Johnson
It is not known whether computerized cognitive assessments, like the CogState battery, are sensitive to preclinical cognitive changes or pathology in people at risk for Alzheimer's disease(AD). In 469 late middle-aged participants from the Wisconsin Registry for Alzheimer's Prevention(mean age 63.8±7 years at testing; 67% female; 39% APOE4+), we examined relationships between a CogState abbreviated battery(CAB) of seven tests and demographic characteristics, traditional paper-based neuropsychological tests as well as a composite cognitive impairment index, cognitive impairment status(determined by consensus review), and biomarkers for amyloid and tau(CSF phosphorylated-tau/Aβ42 and global PET-PiB burden) and neural injury(CSF neurofilament light protein)...
October 18, 2016: Journal of Alzheimer's Disease: JAD
Laura Caberlotto, Luca Marchetti, Mario Lauria, Marco Scotti, Silvia Parolo
Among the genetic factors known to increase the risk of late onset Alzheimer's diseases (AD), the presence of the apolipoproteine e4 (APOE4) allele has been recognized as the one with the strongest effect. However, despite decades of research, the pathogenic role of APOE4 in Alzheimer's disease has not been clearly elucidated yet. In order to investigate the pathogenic action of APOE4, we applied a systems biology approach to the analysis of transcriptomic and genomic data of APOE44 vs. APOE33 allele carriers affected by Alzheimer's disease...
2016: Scientific Reports
Anat Boehm-Cagan, Roni Bar, Ori Liraz, John K Bielicki, Jan O Johansson, Daniel M Michaelson
The allele ɛ4 of apolipoprotein E (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD) and is therefore a promising therapeutic target. Human and animal model studies suggest that apoE4 is hypolipidated; accordingly, we have previously shown that the retinoid X receptor (RXR) agonist bexarotene upregulates ABCA1, the main apoE-lipidating protein, resulting in increased lipidation of apoE4, and the subsequent reversal of the pathological effects of apoE4, namely: accumulation of Aβ42 and hyperphosphorylated tau, as well as reduction in the levels of synaptic markers and cognitive deficits...
October 4, 2016: Journal of Alzheimer's Disease: JAD
Steffen Wolfsgruber, Luca Kleineidam, Michael Wagner, Edelgard Mösch, Horst Bickel, Dagmar Lϋhmann, Annette Ernst, Birgitt Wiese, Susanne Steinmann, Hans-Helmut König, Christian Brettschneider, Tobias Luck, Janine Stein, Siegfried Weyerer, Jochen Werle, Michael Pentzek, Angela Fuchs, Wolfgang Maier, Martin Scherer, Steffi G Riedel-Heller, Frank Jessen
BACKGROUND: It is unknown whether longitudinal stability versus instability in subjective cognitive decline (SCD) is a modifying factor of the association between SCD and risk of incident Alzheimer's disease (AD) dementia. OBJECTIVE: We tested the modifying role of temporal stability of the SCD report on AD dementia risk in cognitively normal elderly individuals. METHODS: We analyzed data of 1,990 cognitively normal participants from the longitudinal AgeCoDe Study...
October 4, 2016: Journal of Alzheimer's Disease: JAD
Won-Suk Chung, Philip B Verghese, Chandrani Chakraborty, Julia Joung, Bradley T Hyman, Jason D Ulrich, David M Holtzman, Ben A Barres
The strongest genetic risk factor influencing susceptibility to late-onset Alzheimer's disease (AD) is apolipoprotein E (APOE) genotype. APOE has three common isoforms in humans, E2, E3, and E4. The presence of two copies of the E4 allele increases risk by ∼12-fold whereas E2 allele is associated with an ∼twofold decreased risk for AD. These data put APOE central to AD pathophysiology, but it is not yet clear how APOE alleles modify AD risk. Recently we found that astrocytes, a major central nervous system cell type that produces APOE, are highly phagocytic and participate in normal synapse pruning and turnover...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
Lebriz Altay, Paula Scholz, Tina Schick, Moritz Felsch, Carel B Hoyng, Anneke I den Hollander, Thomas Langmann, Sascha Fauser
PURPOSE: We evaluated the association of hyperreflective foci (HF) observed in early and intermediate age-related macular degeneration (AMD) with known AMD risk alleles. METHODS: In this pilot case-control study, HF were defined as lesions with reflectivity equal or higher than the retinal pigment epithelium band in spectral domain optical coherence tomography (SDOCT). Hyperreflective foci in the outer nuclear layer and photoreceptor complex were evaluated in 518 individuals with early and intermediate AMD...
August 1, 2016: Investigative Ophthalmology & Visual Science
Nicolette Mary Heinsinger, Mariam Alexandra Gachechiladze, G William Rebeck
Apolipoprotein E (apoE) is associated with lipoproteins in the cerebrospinal fluid (CSF). APOE4 increases and APOE2 decreases the risk for Alzheimer disease (AD) compared to the risk associated with APOE3 Because apoE4 is less efficient at cholesterol efflux than apoE2 or apoE3 in vitro, we hypothesized that APOE genotype may affect apoE particle size in vivo and that these size differences may be related to AD risk. We used nondenaturing gel electrophoresis to test for differences in the size of apoE complexes in human CSF samples of various APOE genotypes and created profiles of each sample to compare the patterns of apoE distribution...
August 11, 2016: Journal of Neuropathology and Experimental Neurology
Ioannis Dafnis, Letta Argyri, Marina Sagnou, Athina Tzinia, Effie C Tsilibary, Efstratios Stratikos, Angeliki Chroni
The apolipoprotein (apo) E4 isoform is the strongest risk factor for late-onset Alzheimer's disease (AD). ApoE4 is more susceptible to proteolysis than apoE2 and apoE3 isoforms and carboxyl-terminal truncated apoE4 forms have been found in AD patients' brain. We have previously shown that a specific apoE4 fragment, apoE4-165, promotes amyloid-peptide beta 42 (Aβ42) accumulation in human neuroblastoma SK-N-SH cells and increased intracellular reactive oxygen species formation, two events considered to occur early in AD pathogenesis...
2016: Scientific Reports
Janina Dose, Patricia Huebbe, Almut Nebel, Gerald Rimbach
The APOE gene is one of currently only two genes that have consistently been associated with longevity. Apolipoprotein E (APOE) is a plasma protein which plays an important role in lipid and lipoprotein metabolism. In humans, there are three major APOE isoforms, designated APOE2, APOE3, and APOE4. Of these three isoforms, APOE3 is most common while APOE4 was shown to be associated with age-related diseases, including cardiovascular and Alzheimer's disease, and therefore an increased mortality risk with advanced age...
2016: Lipids in Health and Disease
Shibani S Mukerji, Joseph J Locascio, Vikas Misra, David R Lorenz, Alex Holman, Anupriya Dutta, Sudhir Penugonda, Steven M Wolinsky, Dana Gabuzda
BACKGROUND: Dyslipidemia and apolipoprotein E4 (APOE ϵ4) allele are risk factors for age-related cognitive decline, but how these risks are modified by human immunodeficiency virus (HIV) infection is unclear. METHODS: In a longitudinal nested study from the Multicenter AIDS Cohort Study, 273 HIV type 1-infected (HIV(+)) men aged 50-65 years with baseline HIV RNA <400 copies/mL and on continuous antiretroviral therapy (ART) in ≥95% of follow-up visits were matched by sociodemographic variables to 516 HIV-uninfected (HIV(-)) controls...
October 15, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Shan Dong, Ran Zhang, Ya-Cheng Ji, Jia-Yin Hao, Wei-Wei Ma, Xu-Dong Chen, Rong Xiao, Huan-Ling Yu
Phytosterols (PSs) are reported to lower the serum total cholesterol and low-density lipoprotein cholesterol concentrations enriched in some fatty foods, such as margarine. However, these high-fat foods are not very suitable for older people. Soy milk is the favorite food for elderly people in China; therefore, we hypothesized that the consumption of soy milk powder supplemented with PSs would decrease the serum cholesterol levels in older Chinese people independent of the genotypes of apolipoprotein E (ApoE)...
August 2016: Nutrition Research
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