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https://www.readbyqxmd.com/read/28106548/does-the-female-advantage-in-verbal-memory-contribute-to-underestimating-alzheimer-s-disease-pathology-in-women-versus-men
#1
Erin E Sundermann, Anat Biegon, Leah H Rubin, Richard B Lipton, Susan Landau, Pauline M Maki
There is a growing recognition of sex differences in Alzheimer's disease (AD). Females show an advantage over males on tests of verbal memory, which are used to diagnose AD and its precursor, amnestic mild cognitive impairment (aMCI). Women retain this advantage in aMCI despite reduced hippocampal volume and temporal lobe glucose metabolism. Here we examined whether this female advantage endures despite evidence of AD-specific pathology, cortical amyloid-β (Aβ) deposition measured with [18F]AV45 (florbetapir) positron emission tomography...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28096372/helical-structure-stability-and-dynamics-in-human-apolipoprotein-e3-and-e4-by-hydrogen-exchange-and-mass-spectrometry
#2
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/28094792/identification-of-a-nuclear-respiratory-factor-1-recognition-motif-in-the-apolipoprotein-e-variant-apoe4-linked-to-alzheimer-s-disease
#3
Anne Urfer-Buchwalder, Roman Urfer
Alzheimer's disease affects tens of millions of people worldwide and its prevalence continues to rise. It is caused by a combination of a subject's heredity, environment, lifestyle, and medical condition. The most significant genetic risk factor for late onset Alzheimer's disease is a variant of the apolipoprotein E gene, APOE4. Here we show that the single nucleotide polymorphism rs429358 that defines APOE4 is located in a short sequence motif repeated several times within exon 4 of apolipoprotein E, reminiscent of the structure of transcriptional enhancers...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088659/altered-cerebral-insulin-response-in-transgenic-mice-expressing-the-epsilon-4-allele-of-the-human-apolipoprotein-e-gene
#4
Marie-Thérèse Traversy, Milène Vandal, Cyntia Tremblay, Marine Tournissac, Ariane Giguère-Rancourt, A David Bennett, Frédéric Calon
Apolipoprotein E epsilon-4 (APOEε4 or APOE4), an allelic variation of the APOE gene, not only increases the risk of developing the late-onset form of Alzheimer's disease (AD), but also influences the outcome of treatment. Indeed, data from clinical studies show that the beneficial effect of insulin on cognition is blunted in APOE4 carriers. To investigate how APOE impacts insulin response, we assessed the effects of an acute insulin injection in APOE3- and APOE4-targeted replacement mice that respectively express the human APOE3 or APOE4 isoform instead of the endogenous murine ApoE protein...
November 30, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28057414/apoe-apoe-receptors-and-the-synapse-in-alzheimer-s-disease
#5
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/28035932/effect-of-vascular-risk-factors-on-the-progression-of-mild-alzheimer-s-disease-and-lewy-body-dementia
#6
Anne Katrine Bergland, Ingvild Dalen, Alf Inge Larsen, Dag Aarsland, Hogne Soennesyn
BACKGROUND: Vascular risk factors (VRF) are associated with an increased risk of neurodegenerative disease. OBJECTIVE: To examine the association between VRF and cognitive decline in patients with Alzheimer's disease (AD) and Lewy body dementia (LBD). METHODS: We included consecutive referrals with mild AD or LBD to dementia clinics in western Norway from 2005 to 2013. The Mini-Mental Status Exam (MMSE) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) were administered at baseline and then annually for up to five years...
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
#7
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
#8
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/28017255/cognitive-deficits-in-non-demented-diabetic-elderly-appear-independent-of-brain-amyloidosis
#9
Gloria C Chiang, Eileen Chang, Sneha Pandya, Amy Kuceyeski, James Hu, Richard Isaacson, Christine Ganzer, Aaron Schulman, Vivian Sobel, Shankar Vallabhajosula, Lisa Ravdin
BACKGROUND: To determine the effects of Type 2 diabetes (DM2) on levels of brain amyloidosis and cognition in a community-dwelling cohort of nondemented elderly individuals. METHODS: 33 subjects (16 DM2, 17 nondiabetic) were prospectively recruited. Subjects underwent a PET scan using the amyloid tracer, Pittsburgh Compound B, and a neuropsychological evaluation. Associations between DM2, brain amyloidosis, and cognition were assessed using multivariate regressions, adjusting for age and APOE4 status...
January 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28003161/apolipoprotein-e4-causes-early-olfactory-network-abnormalities-and-short-term-olfactory-memory-impairments
#10
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/27931262/glymphatic-distribution-of-csf-derived-apoe-into-brain-is-isoform-specific-and-suppressed-during-sleep-deprivation
#11
Thiyagaragan M Achariyar, Baoman Li, Weiguo Peng, Philip B Verghese, Yang Shi, Evan McConnell, Abdellatif Benraiss, Tristan Kasper, Wei Song, Takahiro Takana, David M Holtzman, Maiken Nedergaard, Rashid Deane
BACKGROUND: Apolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it's expressed by many cells but highly expressed by the choroid plexus and the predominant apolipoprotein in cerebrospinal fluid (CSF). The role of apoE in the CSF is unclear. Recently, the glymphatic system was described as a clearance system whereby CSF and ISF (interstitial fluid) is exchanged via the peri-arterial space and convective flow of ISF clearance is mediated by aquaporin 4 (AQP4), a water channel...
December 8, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27922847/apolipoprotein-e-metabolism-and-functions-in-brain-and-its-role-in-alzheimer-s-disease
#12
Fan Liao, Hyejin Yoon, Jungsu Kim
PURPOSE OF REVIEW: APOE4 genotype is the strongest genetic risk factor for Alzheimer's disease. Prevailing evidence suggests that amyloid β plays a critical role in Alzheimer's disease. The objective of this article is to review the recent findings about the metabolism of apolipoprotein E (ApoE) and amyloid β and other possible mechanisms by which ApoE contributes to the pathogenesis of Alzheimer's disease. RECENT FINDINGS: ApoE isoforms have differential effects on amyloid β metabolism...
February 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27917221/the-influence-of-apoe-genotype-on-the-lipid-profile-and-lipoproteins-during-normal-pregnancy-in-a-southern-african-population
#13
Donald Moshen Tanyanyiwa, Adrian David Marais, Pamela Byrnes, Sheena Jones
BACKGROUND: Pregnancy is associated with increases in fasting triglycerides and total cholesterol.1 ApoE isoforms are known to influence the concentration of cholesterol, with apoE2 homozygosity lowering and apoE4 homozygosity raising the cholesterol concentration compared with E3 homozygosity.2 The lipid profiles ApoE status and prevalence of small dense LDL species were evaluated for subjects attending an antenatal clinic. RESULTS: Samples from 690 women aged between 16 and 42 years of age were analyzed during and after pregnancy...
September 2016: African Health Sciences
https://www.readbyqxmd.com/read/27911294/deleterious-effect-of-butyrylcholinesterase-k-variant-in-donepezil-treatment-of-mild-cognitive-impairment
#14
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
#15
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
#16
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
#17
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...
January 2017: Clinical Neuropsychologist
https://www.readbyqxmd.com/read/27830118/variable-phenotypic-expression-of-nonsense-mutation-p-thr5-in-the-apoe-gene
#18
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
#19
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
#20
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...
2017: Journal of Alzheimer's Disease: JAD
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