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Alzheimers and cholesterol

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https://www.readbyqxmd.com/read/28821686/effect-of-simvastatin-on-csf-alzheimer-disease-biomarkers-in-cognitively-normal-adults
#1
Ge Li, Cynthia L Mayer, Daniel Morelli, Steven P Millard, Wendy H Raskind, Eric C Petrie, Monique Cherrier, Anne M Fagan, Murray A Raskind, Elaine R Peskind
OBJECTIVE: To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure. METHODS: Participants were 45-64 years old and statin-naive with normal cognition and normal or mildly elevated cholesterol. Forty-six participants completed the 1-year study per protocol (25 in the simvastatin and 21 in the placebo group)...
August 18, 2017: Neurology
https://www.readbyqxmd.com/read/28815528/alzheimer-disease
#2
Estela Area-Gomez, Eric A Schon
The most widely accepted hypothesis to explain the pathogenesis of Alzheimer disease (AD) is the amyloid cascade, in which the accumulation of extraneuritic plaques and intracellular tangles plays a key role in driving the course and progression of the disease. However, there are other biochemical and morphological features of AD, including altered calcium, phospholipid, and cholesterol metabolism and altered mitochondrial dynamics and function that often appear early in the course of the disease, prior to plaque and tangle accumulation...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28804999/diversity-of-astroglial-responses-across-human-neurodegenerative-disorders-and-brain-aging
#3
Isidro Ferrer
Astrogliopathy refers to alterations of astrocytes occurring in diseases of the nervous system, and it implies the involvement of astrocytes as key elements in the pathogenesis and pathology of diseases and injuries of the central nervous system. Reactive astrocytosis refers to the response of astrocytes to different insults to the nervous system, whereas astrocytopathy indicates hypertrophy, atrophy/degeneration and loss of function and pathological remodeling occurring as a primary cause of a disease or as a factor contributing to the development and progression of a particular disease...
September 2017: Brain Pathology
https://www.readbyqxmd.com/read/28760925/the-cholesterol-ester-cycle-regulates-signalling-complexes-and-synapse-damage-caused-by-amyloid-%C3%AE
#4
Ewan West, Craig Osborne, Clive Bate
Cholesterol is required for the formation and function of some signalling platforms. In synaptosomes amyloid-β (Aβ) oligomers, the causative agent in Alzheimer's disease, bind to cellular prion proteins (PrP(C)) resulting in increased cholesterol concentrations, translocation of cytoplasmic phospholipase A2 (cPLA2) to lipid rafts and activation of cPLA2 The formation of Aβ:PrP(C) complexes was controlled by the cholesterol ester cycle. Aβ activated cholesterol ester hydrolases which released cholesterol from stores of cholesterol esters and stabilised Aβ:PrP(C) complexes resulting in activated cPLA2 Conversely, cholesterol esterification reduced cholesterol concentrations causing the dispersal of Aβ:PrP(C) complexes...
July 31, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28758631/statins-are-ineffective-at-reducing-neuroinflammation-or-prolonging-survival-in-scrapie-infected-mice
#5
James A Carroll, Brent Race, Katie Phillips, James F Striebel, Bruce Chesebro
Neuroinflammation is a prominent component of several neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, tauopathies, amyotrophic lateral sclerosis and prion diseases. In such conditions, the ability to decrease neuroinflammation by drug therapy may influence disease progression. Statins have been used to treat hyperlipidemia as well as reduce neuroinflammation and oxidative stress in various tissues. In previous studies, treatment of scrapie-infected mice with the type 1 statins, simvastatin or pravastatin, showed a small beneficial effect on survival time...
July 31, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28749476/the-wide-genetic-landscape-of-clinical-frontotemporal-dementia-systematic-combined-sequencing-of-121-consecutive-subjects
#6
Cornelis Blauwendraat, Carlo Wilke, Javier Simón-Sánchez, Iris E Jansen, Anika Reifschneider, Anja Capell, Christian Haass, Melissa Castillo-Lizardo, Saskia Biskup, Walter Maetzler, Patrizia Rizzu, Peter Heutink, Matthis Synofzik
PurposeTo define the genetic spectrum and relative gene frequencies underlying clinical frontotemporal dementia (FTD).MethodsWe investigated the frequencies and mutations in neurodegenerative disease genes in 121 consecutive FTD subjects using an unbiased, combined sequencing approach, complemented by cerebrospinal fluid Aβ1-42 and serum progranulin measurements. Subjects were screened for C9orf72 repeat expansions, GRN and MAPT mutations, and, if negative, mutations in other neurodegenerative disease genes, by whole-exome sequencing (WES) (n = 108), including WES-based copy-number variant (CNV) analysis...
July 27, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28744197/neuronal-cholesterol-accumulation-induced-by-cyp46a1-down-regulation-in-mouse-hippocampus-disrupts-brain-lipid-homeostasis
#7
Sophie Ayciriex, Fathia Djelti, Sandro Alves, Anne Regazzetti, Mathieu Gaudin, Jennifer Varin, Dominique Langui, Ivan Bièche, Eloise Hudry, Delphine Dargère, Patrick Aubourg, Nicolas Auzeil, Olivier Laprévote, Nathalie Cartier
Impairment in cholesterol metabolism is associated with many neurodegenerative disorders including Alzheimer's disease (AD). However, the lipid alterations underlying neurodegeneration and the connection between altered cholesterol levels and AD remains not fully understood. We recently showed that cholesterol accumulation in hippocampal neurons, induced by silencing Cyp46a1 gene expression, leads to neurodegeneration with a progressive neuronal loss associated with AD-like phenotype in wild-type mice. We used a targeted and non-targeted lipidomics approach by liquid chromatography coupled to high-resolution mass spectrometry to further characterize lipid modifications associated to neurodegeneration and cholesterol accumulation induced by CYP46A1 inhibition...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28734741/beneficial-effects-of-tqrf-and-tq-nano-and-conventional-emulsions-on-memory-deficit-lipid-peroxidation-total-antioxidant-status-antioxidants-genes-expression-and-soluble-a%C3%AE-levels-in-high-fat-cholesterol-diet-induced-rats
#8
Norsharina Ismail, Maznah Ismail, Nur Hanisah Azmi, Muhammad Firdaus Abu Bakar, Zhang Yida, Johnson Stanslas, Dahiru Sani, Hamidon Basri, Maizaton Atmadini Abdullah
The study determined the effect of thymoquinone rich fraction (TQRF) and thymoquinone (TQ) in the forms of nano- and conventional emulsions on learning and memory, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble β-amyloid (Aβ) levels in rats fed with a high fat-cholesterol diet (HFCD). The TQRF was extracted from Nigella sativa seeds using a supercritical fluid extraction system and prepared into nanoemulsion, which later named as TQRF nanoemulsion (TQRFNE). Meanwhile, TQ was acquired commercially and prepared into thymoquinone nanoemulsion (TQNE)...
July 20, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28731431/association-between-cholesterol-exposure-and-neuropathological-findings-the-act-study
#9
Brianne M Bettcher, M Colin Ard, Bruce R Reed, Andreana Benitez, Amanda Simmons, Eric B Larson, Josh A Sonnen, Thomas J Montine, Ge Li, C Dirk Keene, Paul K Crane, Dan Mungas
We characterized the relationship between late life cholesterol exposure and neuropathological outcomes in a community-based, older adult cohort. Adult Changes in Thought (ACT) is a cohort study that enrolls consenting, randomly selected, non-demented people aged ≥65 from a healthcare delivery system. We used late life HDL and total cholesterol lab values from Group Health computerized records, and calculated HDL and non-HDL levels. We evaluated neuropathological outcomes of Alzheimer's disease, cerebral amyloid angiopathy, vascular brain injury, and Lewy body disease...
July 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28725889/cholesterol-lowering-by-pediococcus-acidilactici-lab4-and-lactobacillus-plantarum-lab12-in-adult-zebrafish-is-associated-with-improved-memory-and-involves-an-interplay-between-npc1l1-and-abca1
#10
Fei Tieng Lim, Siong Meng Lim, Kalavathy Ramasamy
This study assessed the cholesterol lowering effect of Pediococcus acidilactici LAB4 and Lactobacillus plantarum LAB12 using adult zebrafish. Animals were fed with a high cholesterol diet (HCD) with/without LAB for seven weeks. Serum and liver cholesterol was quantified using colorimetric and dye staining methods. Expressions of npc1l1 and abca1 in the liver and intestine and appa in the brain were quantified using RT-PCR. Serum and liver cholesterol was significantly lowered in LAB4- and LAB12-fed zebrafish (≤64% and ≤71%, respectively), with reduced liver cholesterol deposition...
August 1, 2017: Food & Function
https://www.readbyqxmd.com/read/28722194/effects-of-cholesterol-transport-inhibitor-u18666a-on-app-metabolism-in-rat-primary-astrocytes
#11
Hongyan Yang, Yanlin Wang, Satyabrata Kar
Amyloid β (Aβ) peptides generated from the amyloid precursor protein (APP) play an important role in the degeneration of neurons and development of Alzheimer's disease (AD). Current evidence indicates that high levels of cholesterol-which increase the risk of developing AD-can influence Aβ production in neurons. However, it remains unclear how altered level/subcellular distribution of cholesterol in astrocytes can influence APP metabolism. In this study, we evaluated the effects of cholesterol transport inhibitor U18666A-a class II amphiphile that triggers redistribution of cholesterol within the endosomal-lysosomal (EL) system-on APP levels and metabolism in rat primary cultured astrocytes...
July 19, 2017: Glia
https://www.readbyqxmd.com/read/28718623/a-multimodal-spectroscopic-imaging-method-to-characterize-the-metal-and-macromolecular-content-of-proteinaceous-aggregates-amyloid-plaques
#12
Kelly L Summers, Nicholas Fimognari, Ashley Hollings, Mitchell Kiernan, Virginie Lam, Rebecca J Tidy, David Paterson, Mark J Tobin, Ryu Takechi, Graham N George, Ingrid J Pickering, John C Mamo, Hugh H Harris, Mark J Hackett
Alzheimer's disease (AD) is a major international health and economic concern. A key pathological feature of AD is so-called "amyloid-β-plaques", or "Aβ-plaques", which are deposits of aggregated protein, enriched with the Aβ fragment of amyloid precursor protein. Despite their name, the deposits are not pure Aβ and have a heterogeneous, chemically complex composition that can include multiple proteins, lipids, and metal ions (Fe, Cu, or Zn). Despite extensive research, it is still uncertain whether Aβ-plaques are a cause or a consequence of AD pathology...
August 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28663202/low-ldl-cholesterol-pcsk9-and-hmgcr-genetic-variation-and-risk-of-alzheimer-s-disease-and-parkinson-s-disease-mendelian-randomisation-study
#13
(no author information available yet)
No abstract text is available yet for this article.
June 29, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28660589/on-electrochemical-methods-for-determination-of-protein-lipid-interaction
#14
Zhiping Hu, Yanli Mao
Amyloid-β (Aβ) peptides are important and reliable molecular biomarkers for the diagnosis and prognosis of Alzheimer's disease. Aggregation and fibrillization of Aβ peptides on ganglioside GM1 (GM1)-containing lipid membranes is considered a cause of neurodegenerative disease. Because GM1 is abundant in the central nervous system and plays a key role in the aggregation of Aβ, the interaction of Aβ with supported planar lipid bilayers (SPBs) containing GM1 is of great significance. We have prepared SPBs containing GM1 in order to study the electrochemical characteristics of GM1/sphingomyelin/cholesterol SPBs and their interaction with Aβ(1-40) by cyclic voltammetry and electrochemical impedance spectroscopy (EIS), which proves that electrochemical is a promising method for analyzing the interaction between peptides and lipid membranes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28660014/apolipoprotein-e-a-multifunctional-protein-with-implications-in-various-pathologies-as-a-result-of-its-structural-features
#15
REVIEW
Irina Florina Tudorache, Violeta Georgeta Trusca, Anca Violeta Gafencu
Apolipoprotein E (apoE), a 34 kDa glycoprotein, mediates hepatic and extrahepatic uptake of plasma lipoproteins and cholesterol efflux from lipid-laden macrophages. In humans, three structural different apoE isoforms occur, with subsequent functional changes and pathological consequences. Here, we review data supporting the involvement of apoE structural domains and isoforms in normal and altered lipid metabolism, cardiovascular and neurodegenerative diseases, as well as stress-related pathological states...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28655608/cholesterol-metabolizing-enzyme-cytochrome-p450-46a1-as-a-pharmacologic-target-for-alzheimer-s-disease
#16
Natalia Mast, Aicha Saadane, Ana Valencia-Olvera, James Constans, Erin Maxfield, Hiroyuki Arakawa, Young Li, Gary Landreth, Irina A Pikuleva
Cytochrome P450 46A1 (CYP46A1 or cholesterol 24-hydroxylase) controls cholesterol elimination from the brain and plays a role in higher order brain functions. Genetically enhanced CYP46A1 expression in mouse models of Alzheimer's disease mitigates the manifestations of this disease. We enhanced CYP46A1 activity pharmacologically by treating 5XFAD mice, a model of rapid amyloidogenesis, with a low dose of the anti-HIV medication efavirenz. Efavirenz was administered from 1 to 9 months of age, and mice were evaluated at specific time points...
September 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28620033/scissor-sisters-regulation-of-adam10-by-the-tspanc8-tetraspanins
#17
REVIEW
Alexandra L Matthews, Justyna Szyroka, Richard Collier, Peter J Noy, Michael G Tomlinson
A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitously expressed transmembrane protein which is essential for embryonic development through activation of Notch proteins. ADAM10 regulates over 40 other transmembrane proteins and acts as a 'molecular scissor' by removing their extracellular regions. ADAM10 is also a receptor for α-toxin, a major virulence factor of Staphylococcus aureus Owing to the importance of its substrates, ADAM10 is a potential therapeutic target for cancer, neurodegenerative diseases such as Alzheimer's and prion diseases, bacterial infection and inflammatory diseases such as heart attack, stroke and asthma...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28593141/glycosyl-chains-and-25-hydroxycholesterol-contribute-to-the-intracellular-transport-of-amyloid-beta-a%C3%AE-42-in-jurkat-t-cells
#18
Neha Sharma, KeangOK Baek, Huong T T Phan, Naofumi Shimokawa, Masahiro Takagi
Amyloid beta (Aβ) is a peptide responsible for the development of Alzheimer's disease (AD). Misfolding and accumulation of endogenous Aβ can lead to neural cell apoptosis through endoplasmic reticulum (ER) stress. Added exogenous Aβ can also result in ER stress, leading to neurotoxicity and apoptosis, which is identical to that caused by the endogenous peptide. We have speculated that the endocytic transport of Aβ causes ER stress and have previously shown that the oxysterol, in particular, 7-ketocholesterol (7-keto) induces more surface interaction between Aβ-42 and Jurkat cells than cholesterol...
June 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28584559/schisandrae-fructus-reduces-symptoms-of-4-vinylcyclohexene-diepoxide-induced-ovarian-failure-in-mice
#19
Dasom Shin, Jinhee Ha, Seong Bin Hong, Geun-Hyung Kang, Deok-Sang Hwang, Hyunsu Bae
Menopause is associated with a decrease in the level of sex hormones such as ovarian estradiol and progesterone and can cause various symptoms such as depression, hot flash, fatigue, heart palpitations, and headache. Furthermore, there is a risk of developing complications such as osteoporosis, cardiovascular diseases, Alzheimer's disease, and ovarian cancer. Schisandrae Fructus (SF) is widely used in Korean medicine as a cure for such complications. This study was conducted to evaluate the therapeutic effects of SF against menopause symptoms associated with follicle depletion caused by the industrial chemical 4-vinylcyclohexene diepoxide (VCD) in mice...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28582856/lipidomic-profiles-in-diabetes-and%C3%A2-dementia
#20
Kevin Huynh, Ralph N Martins, Peter J Meikle
Lipids are a diverse class of hydrophobic and amphiphilic molecules which make up the bulk of most biological systems and are essential for human life. The role of lipids in health and disease has been recognized for many decades, as evidenced by the early identification of cholesterol as an important risk factor of heart disease and the development and introduction of statins as a one of the most successful therapeutic interventions to date. While several studies have demonstrated an increased risk of dementia, including Alzheimer's disease (AD), in those with diabetes mellitus, the nature of this risk is not well understood...
2017: Journal of Alzheimer's Disease: JAD
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