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Alzheimers and cholesterol

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https://www.readbyqxmd.com/read/28212683/evidence-for-benefit-of-statins-to-modify-cognitive-decline-and-risk-in-alzheimer-s-disease
#1
Nophar Geifman, Roberta Diaz Brinton, Richard E Kennedy, Lon S Schneider, Atul J Butte
BACKGROUND: Despite substantial research and development investment in Alzheimer's disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, β-amyloid and AD, and several studies have shown a reduced risk for AD and dementia in populations treated with statins. However, while some clinical trials evaluating statins in general AD populations have been conducted, these resulted in no significant therapeutic benefit. By focusing on subgroups of the AD population, it may be possible to detect endotypes responsive to statin therapy...
February 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28206976/lipid-and-alzheimer-s-disease-genes-associated-with-healthy-aging-and-longevity-in-healthy-oldest-old
#2
Lauren C Tindale, Stephen Leach, John J Spinelli, Angela R Brooks-Wilson
Several studies have found that long-lived individuals do not appear to carry lower numbers of common disease-associated variants than ordinary people; it has been hypothesized that they may instead carry protective variants. An intriguing type of protective variant is buffering variants that protect against variants that have deleterious effects. We genotyped 18 variants in 15 genes related to longevity or healthy aging that had been previously reported as having a gene-gene interaction or buffering effect...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205173/measurement-of-mitochondrial-cholesterol-import-using-a-mitochondria-targeted-cyp11a1-fusion-construct
#3
Barry E Kennedy, Mark Charman, Barbara Karten
All animal membranes require cholesterol as an essential regulator of biophysical properties and function, but the levels of cholesterol vary widely among different subcellular compartments. Mitochondria, and in particular the inner mitochondrial membrane, have the lowest levels of cholesterol in the cell. Nevertheless, mitochondria need cholesterol for membrane maintenance and biogenesis, as well as oxysterol, steroid, and hepatic bile acid production. Alterations in mitochondrial cholesterol have been associated with a range of pathological conditions, including cancer, hepatosteatosis, cardiac ischemia, Alzheimer's, and Niemann-Pick Type C Disease...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28205163/hybrid-in-silico-in-vitro-approaches-for-the-identification-of-functional-cholesterol-binding-domains-in-membrane-proteins
#4
Coralie Di Scala, Jacques Fantini
In eukaryotic cells, cholesterol is an important regulator of a broad range of membrane proteins, including receptors, transporters, and ion channels. Understanding how cholesterol interacts with membrane proteins is a difficult task because structural data of these proteins complexed with cholesterol are scarce. Here, we describe a dual approach based on in silico studies of protein-cholesterol interactions, combined with physico-chemical measurements of protein insertion into cholesterol-containing monolayers...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28188218/focal-solute-trapping-and-global-glymphatic-pathway-impairment-in-a-murine-model-of-multiple-microinfarcts
#5
Minghuan Wang, Fengfei Ding, SaiYue Deng, Xuequn Guo, Wei Wang, Jeffrey J Iliff, Maiken Nedergaard
Microinfarcts occur commonly in the aging brain as a consequence of diffuse embolic events and are associated with the development of vascular dementia and Alzheimer's disease. Yet the manner in which disperse microscopic lesions reduce global cognitive function and increase the risk for Alzheimer's disease is unclear. The glymphatic system, which is a brain-wide perivascular network that supports the recirculation of CSF through the brain parenchyma, facilitates the clearance of interstitial solutes including amyloid beta and tau...
February 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28170429/cholesterol-contributes-to-dopamine-neuronal-loss-in-mptp-mouse-model-of-parkinson-s-disease-involvement-of-mitochondrial-dysfunctions-and-oxidative-stress
#6
Rajib Paul, Amarendranath Choudhury, Sanjeev Kumar, Anirudha Giri, Rajat Sandhir, Anupom Borah
Hypercholesterolemia is a known contributor to the pathogenesis of Alzheimer's disease while its role in the occurrence of Parkinson's disease (PD) is only conjecture and far from conclusive. Altered antioxidant homeostasis and mitochondrial functions are the key mechanisms in loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain in PD. Hypercholesterolemia is reported to cause oxidative stress and mitochondrial dysfunctions in the cortex and hippocampus regions of the brain in rodents...
2017: PloS One
https://www.readbyqxmd.com/read/28164772/clinical-and-environmental-correlates-of-serum-bdnf-a-descriptive-study-with-plausible-implications-for-ad-research
#7
Galit Weinstein, Sarah R Preis, Alexa S Beiser, Bernhard Kaess, Tai C Chen, Claudia Satizabal, Faisal Rahman, Emelia J Benjamin, Vasan S Ramachandran, Sudha Seshadri
BACKGROUND: Brain derived neurotrophic factor (BDNF) may play a central role in the pathogenesis of Alzheimer's disease (AD) through neurotrophic effects on basal cholinergic neurons. Reduced serum levels of BDND are observed among AD patients and may predict AD risk. Nevertheless, knowledge about factors associated with its levels in blood is lacking. OBJECTIVE: To identify clinical and demographic correlated of serum BDNF levels . METHODS: BDNF was measured from serum collected between 1992-1996 and 1998-2001 in participants from the Original and Offspring cohorts of the Framingham Study, respectively...
February 2, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28153452/adenosine-receptors-modulators-of-lipid-availability-that-are-controlled-by-lipid-levels
#8
REVIEW
Andrea Leiva, Enrique Guzmán-Gutiérrez, Susana Contreras-Duarte, Bárbara Fuenzalida, Claudette Cantin, Lorena Carvajal, Rocío Salsoso, Jaime Gutiérrez, Fabián Pardo, Luis Sobrevia
Adenosine as well as agonists and antagonists for the four adenosine receptor subtypes (A1R, A2AR, A2BR and A3R) play a role in several key physiological and pathophysiological processes, including the regulation of vascular tone, thrombosis, immune response, inflammation, and angiogenesis. This review focuses on the adenosine-mediated regulation of lipid availability in the cell and in the systemic circulation as well in humans and animal models. Therefore, adenosine, mainly by acting on A1R, inhibits lipolysis activity, leading to reduction of the circulating fatty acid levels...
January 30, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28151011/cardiovascular-risk-factors-and-glucose-tolerance-in-midlife-and-risk-of-cognitive-disorders-in-old-age-up-to-a-49-year-follow-up-of-the-helsinki-businessmen-study
#9
Kirsi Rantanen, Arto Y Strandberg, Veikko V Salomaa, Kaisu H Pitkälä, Reijo S Tilvis, Pentti J Tienari, Timo E Strandberg
PURPOSE: To compare midlife predictors of old age dementia with or without concomitant atherosclerotic cardiovascular disease (ASCVD). DESIGN: In the Helsinki Businessmen Study (men born in 1919-1934, n = 3309) death certificates (n = 1885) during up to 49-year follow-up (through December 31, 2013) were screened for dementia (n = 365) and ASCVD, and categorized as 1) AD without ASCVD ("pure" AD, n = 93), 2) AD+ASCVD (n = 126), 3) Vascular dementia (VD, n = 82), 4) Other or undefined etiology (n = 64)...
February 2, 2017: Annals of Medicine
https://www.readbyqxmd.com/read/28130408/hormone-deprivation-alters-mitochondrial-function-and-lipid-profile-in-the-hippocampus
#10
Sandra Zárate, Mariana Astiz, Natalia Magnani, Mercedes Imsen, Florencia Merino, Silvia Álvarez, Analía Reinés, Adriana Seilicovich
Mitochondrial dysfunction is a common hallmark in aging. In the female, reproductive senescence is characterized by loss of ovarian hormones, many of whose neuroprotective effects converge upon mitochondria. Mitochondria functional integrity is dependent on membrane fatty acid and phospholipid composition, parameters also affected during aging. The effect of long-term ovarian hormone deprivation upon mitochondrial function and its putative association with changes in mitochondrial membrane lipid profile in the hippocampus, an area primarily affected during aging and highly responsive to ovarian hormones, is unknown...
January 27, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28116245/7-ketocholesterol-induces-apoptosis-of-mc3t3-e1-cells-associated-with-reactive-oxygen-species-generation-endoplasmic-reticulum-stress-and-caspase-3-7-dependent-pathway
#11
Yuta Sato, Noriko Ishihara, Daiji Nagayama, Atsuhito Saiki, Ichiro Tatsuno
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of bone fractures without reduction of bone mineral density. The cholesterol oxide 7-ketocholesterol (7KCHO) has been implicated in numerous diseases such as atherosclerosis, Alzheimer's disease, Parkinson's disease, cancer, age-related macular degeneration and T2DM. In the present study, 7KCHO decreased the viability of MC3T3-E1 cells, increased reactive oxygen species (ROS) production and apoptotic rate, and upregulated the caspase-3/7 pathway...
March 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28111291/cd36-gene-polymorphism-is-associated-with-alzheimer-s-disease
#12
Omar Šerý, Jana Janoutová, Laura Ewerlingová, Alice Hálová, Jan Lochman, Vladimír Janout, Naim A Khan, Vladimir J Balcar
CD36 gene encodes a membrane glycoprotein (type B scavenger receptor) present on the surface of many types of cells and having multiple cellular functions ranging from angiogenesis to gustatory perception of fatty acids. Using a case control genetic association approach we have analyzed selected single nucleotide polymorphisms (SNP's) in a total of 859 patients with Alzheimer's disease (AD) and controls and have identified the allele T in rs3211893 polymorphism of CD36 gene as significantly increasing the risk of AD...
January 19, 2017: Biochimie
https://www.readbyqxmd.com/read/28106559/abca1-deficiency-affects-basal-cognitive-deficits-and-dendritic-density-in-mice
#13
Nicholas F Fitz, Alexis Y Carter, Victor Tapias, Emilie L Castranio, Ravindra Kodali, Iliya Lefterov, Radosveta Koldamova
ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-free apolipoproteins and regulates the generation of high density lipoproteins. Previously, we have shown that lack of Abca1 significantly increases amyloid deposition and cognitive deficits in Alzheimer's disease model mice expressing human amyloid-β protein precursor (APP). The goal of this study was to determine if ABCA1 plays a role in memory deficits caused by amyloid-β (Aβ) oligomers and examine neurite architecture of pyramidal hippocampal neurons...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28102375/the-dynamic-binding-of-cholesterol-to-the-multiple-sites-of-c99-as-revealed-by-coarse-grained-and-all-atom-simulations
#14
Cheng-Dong Li, Qin Xu, Ruo-Xu Gu, Jing Qu, Dong-Qing Wei
It is generally believed that the etiology of Alzheimer's disease (AD) is closely related to the amyloid-β polypeptides, produced from γ-secretase cleavage of C99. There is preliminary evidence that cholesterol directly activates γ-secretase cleavage of C99 through mechanisms that have not been understood so far. In this article, coarse-grained (CG) and all-atom (AT) simulations were employed to investigate the association between C99 and cholesterol, which is essential for our understanding of the role of cholesterol in the amyloidogenic pathway...
February 1, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28099631/associations-of-cerebrovascular-metabolism-genotypes-with-neuropsychiatric-symptoms-and-age-at-onset-of-alzheimer-s-disease-dementia
#15
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
#16
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 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28077650/melanin-or-melanin-like-substance-interacts-with-the-n-terminal-portion-of-prion-protein-and-inhibits-abnormal-prion-protein-formation-in-prion-infected-cells
#17
Taichi Hamanaka, Keiko Nishizawa, Yuji Sakasegawa, Ayumi Oguma, Kenta Teruya, Hiroshi Kurahashi, Hideyuki Hara, Suehiro Sakaguchi, Katsumi Doh-Ura
Prion diseases are progressive fatal neurodegenerative illnesses caused by the accumulation of transmissible abnormal prion protein (PrP). To find treatments for prion diseases, we searched for substances from natural resources that inhibit abnormal PrP formation in prion-infected cells. We found that high-molecular-weight components from insect cuticle extracts reduced abnormal PrP levels. The chemical nature of these components was consistent with that of melanin. In fact, synthetic melanin produced from tyrosine or 3-hydroxy-l-tyrosine inhibited abnormal PrP formation...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28062666/cyclodextrin-has-conflicting-actions-on-autophagy-flux-in-vivo-in-brains-of-normal-and-alzheimer-model-mice
#18
Dun-Sheng Yang, Philip Stavrides, Asok Kumar, Ying Jiang, Panaiyur S Mohan, Masuo Ohno, Kostantin Dobrenis, Cristin D Davidson, Mitsuo Saito, Monika Pawlik, Chunfeng Huo, Steven U Walkley, Ralph A Nixon
2-hydroxypropyl-β-cyclodextrin (CYCLO), a modifier of cholesterol efflux from cellular membrane and endo-lysosomal compartments, reduces lysosomal lipid accumulations and has therapeutic effects in animal models of Niemann-Pick disease type C and several other neurodegenerative states. Here, we investigated CYCLO effects on autophagy in wild-type mice and TgCRND8 mice - an Alzheimer's Disease (AD) model exhibiting β-amyloidosis, neuronal autophagy deficits leading to protein and lipid accumulation within greatly enlarged autolysosomes...
January 5, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28059793/resveratrol-intervenes-in-the-cholesterol-and-isoprenoid-mediated-amyloidogenic-processing-of-a%C3%AE-pp-in-familial-alzheimer-s-disease
#19
Mohan Sathya, Ponnusamy Moorthi, Palanisamy Premkumar, Mahesh Kandasamy, Kesavan Swaminathan Jayachandran, Muthuswamy Anusuyadevi
Deterioration of cholesterol metabolism has recently been a frontier subject of investigation in the field of Alzheimer's disease (AD). Though amyloid-β protein precursor (AβPP) primes the pathological cascade, changes in cholesterol levels and its intermediates, geranyl geranyl pyrophosphate and farnesyl pyrophosphate, is expected to have a different consequence on AβPP processing and amyloid-β (Aβ) generation. However, the use of statins (HMG-COA reductase inhibitor) has been widely implicated in slowing down the pathogenic progression of AD, while the epidemiological reports on its biological effect remains controversial...
December 3, 2017: Journal of Alzheimer's Disease: JAD
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
#20
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
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