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Alzheimers and cholesterol

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https://www.readbyqxmd.com/read/29238218/breaking-the-cycle-cholesterol-cycling-and-synapse-damage-in-response-to-amyloid-%C3%AE
#1
Clive Bate
Soluble amyloid-β (Aβ) oligomers, a key driver of pathogenesis in Alzheimer disease, bind to cellular prion proteins (PrPC) expressed on synaptosomes resulting in increased cholesterol concentrations, movement of cytoplasmic phospholipase A2 (cPLA2) to lipid rafts and activation of cPLA2. The formation of Aβ-PrPC-cPLA2 complexes was controlled by the cholesterol ester cycle. Thus, Aβ activated cholesterol ester hydrolases which released cholesterol from stores of cholesterol esters; the increased cholesterol concentrations stabilised Aβ-PrPC-cPLA2 complexes...
2017: Journal of Experimental Neuroscience
https://www.readbyqxmd.com/read/29223352/atp-binding-cassette-transporter-2-abca2-as-a-therapeutic-target
#2
REVIEW
Warren Davis, Kenneth D Tew
The ATP binding cassette transporter ABCA2 is primarily an endolysosomal membrane protein that demonstrates pleiotropic functionalities, coalescing around the maintenance of homeostasis of sterols, sphingolipids and cholesterol. It is most highly expressed in brain tissue and ABCA2 knockout mice express neurological defects consistent with aberrant myelination. Increased expression of the transporter has been linked with resistance to cancer drugs, particularly those possessing a steroid backbone and gene expression (in concert with other genes involved in cholesterol metabolism) was found to be regulated by sterols...
December 6, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29208493/almond-hazelnut-and-walnut-three-nuts-for-neuroprotection-in-alzheimer-s-disease-a-neuropharmacological-review-of-their-bioactive-constituents
#3
REVIEW
Narjes Gorji, Reihaneh Moeini, Zahra Memariani
An increase in the prevalence of Alzheimer's disease (AD) as a multifactorial neurodegenerative disorder is an almost obvious issue in the world. Researches on natural products for finding effective drugs to prevent the disease are in progress. There is special attention to the three types of nuts including almond, hazelnut and walnut in manuscripts of traditional Persian medicine (PM) as preventive agents against brain's atrophy and memory loss. The purpose of this study is a pharmacological review of their bioactive constituents and introducing the value of these nuts as effective supplements and natural medicinal foods in AD patients...
December 2, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29204109/intracellular-cholesterol-trafficking-and-impact-in-neurodegeneration
#4
REVIEW
Fabian Arenas, Carmen Garcia-Ruiz, Jose C Fernandez-Checa
Cholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhibits a heterogeneous regulation in distinct brain cell populations. Due to the key role of cholesterol in brain physiology and function, alterations in cholesterol homeostasis and levels have been linked to brain diseases and neurodegeneration...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29202360/enhanced-capillary-electrophoretic-screening-of-alzheimer-based-on-direct-apolipoprotein-e-genotyping-and-one-step-multiplex-pcr
#5
Nain Woo, Su-Kang Kim, Yucheng Sun, Seong Ho Kang
Human apolipoprotein E (ApoE) is associated with high cholesterol levels, coronary artery disease, and especially Alzheimer's disease. In this study, we developed an ApoE genotyping and one-step multiplex polymerase chain reaction (PCR) based-capillary electrophoresis (CE) method for the enhanced diagnosis of Alzheimer's. The primer mixture of ApoE genes enabled the performance of direct one-step multiplex PCR from whole blood without DNA purification. The combination of direct ApoE genotyping and one-step multiplex PCR minimized the risk of DNA loss or contamination due to the process of DNA purification...
November 27, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29193679/increased-levels-of-27-hydroxycholesterol-induced-by-dietary-cholesterol-in-brain-contribute-to-the-learning-and-memory-impairment-in-rats
#6
Xiaona Zhang, Chenyan Lv, Yu An, Quanri Liu, Hongguo Rong, Lingwei Tao, Ying Wang, Yushan Wang, Rong Xiao
SCOPE: Dietary cholesterol has been shown to play a role in the development of Alzheimer's disease (AD). We have proposed that oxysterol especially 27-hydroxycholesterol (27-OHC) may play a potential role in β-amyloid peptides (Aβ) production and accumulation during AD progression. METHODS AND RESULTS: To investigate the mechanisms of dietary cholesterol and 27-OHC on learning and memory impairment, male Sprague-Dawley rats were fed with cholesterol diet with or without 27-OHC synthetase inhibitor (anastrozole) injection...
November 28, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29182710/objective-cognitive-impairment-and-progression-to-dementia-in-women-the-prospective-epidemiological-risk-factor-study
#7
J Skov Neergaard, K Dragsbæk, C Christiansen, M Asser Karsdal, S Brix, K Henriksen
BACKGROUND: Identification of subjects with a progressive disease phenotype is an urgent need in the pharmaceutical industry where most of the recent clinical trials in Alzheimer's disease have failed. OBJECTIVES: The objective of this study was to identify subgroups of individuals with objective cognitive impairment (OCI), who were most likely to progress to dementia and to identify the risk factors associated with progression. DESIGN: Prospective cohort study...
2017: Journal of Prevention of Alzheimer's Disease
https://www.readbyqxmd.com/read/29148800/size-and-shape-of-amyloid-fibrils-induced-by-ganglioside-nanoclusters-role-of-sialyl-oligosaccharide-in-fibril-formation
#8
Teruhiko Matsubara, Masaya Nishihara, Hanaki Yasumori, Mako Nakai, Katsuhiko Yanagisawa, Toshinori Sato
Ganglioside-enriched microdomains in the presynaptic neuronal membrane play a key role in the initiation of amyloid ß-protein (Aß) assembly related to Alzheimer's disease. We previously isolated lipids from a detergent-resistant membrane microdomain fraction of synaptosomes prepared from aged mouse brain and found that spherical Aß assemblies were formed on Aß-sensitive ganglioside nanoclusters (ASIGN) of reconstituted lipid bilayers in the synaptosomal fraction. In the present study, we investigated the role of oligosaccharides in Aß fibril formation induced by ganglioside-containing mixed lipid membranes that mimic the features of ASIGN...
November 17, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29146683/pcsk9-variants-ldl-cholesterol-and-neurocognitive-impairment-the-reasons-for-geographic-and-racial-differences-in-stroke-regards-study
#9
Matthew T Mefford, Robert S Rosenson, Mary Cushman, Michael E Farkouh, Leslie A McClure, Virginia G Wadley, Marguerite R Irvin, Vera A Bittner, Monika M Safford, Ransi Somaratne, Keri L Monda, Paul Muntner, Emily B Levitan
Background -Despite concerns about adverse neurocognitive events raised by prior trials, pharmacologic PCSK9 inhibition was not associated with neurocognitive effects in a recent phase 3 randomized trial. PCSK9 loss-of-function (LOF) variants that result in life-long exposure to low LDL-C can provide information on the potential long-term effects of low LDL-C on neurocognitive impairment and decline. Methods -We investigated the association between PCSK9 LOF variants and neurocognitive impairment and decline among African-American REasons for Geographic and Racial Differences in Stroke (REGARDS) study participants with (n=241) and without (n=10,454) C697X or Y142X LOF variants...
November 16, 2017: Circulation
https://www.readbyqxmd.com/read/29132216/curcumin-decreases-hyperphosphorylation-of-tau-by-down-regulating-caveolin-1-gsk-3%C3%AE-in-n2a-app695swe-cells-and-app-ps1-double-transgenic-alzheimer-s-disease-mice
#10
Jieyun Sun, Xiong Zhang, Chen Wang, Zhipeng Teng, Yu Li
Caveolin-1, the marker protein of membranal caveolae, is not only involved in cholesterol regulation, but also participates in the cleavage of amyloid [Formula: see text]-protein precursor (APP) and the generation of [Formula: see text]-amyloid peptide. It has been reported to be tightly related with Tau. In our previous studies, curcumin has been confirmed to play a neuroprotective role in Alzheimer's disease (AD), but its effects on Caveolin-1, Tau and their correlation, and the mechanism is still unknown...
November 13, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29125484/general-practice-clinical-data-help-identify-dementia-hotspots-a-novel-geospatial-analysis-approach
#11
Nasser Bagheri, Kinley Wangdi, Nicolas Cherbuin, Kaarin J Anstey
We have a poor understanding of whether dementia clusters geographically, how this occurs, and how dementia may relate to socio-demographic factors. To shed light on these important questions, this study aimed to compute a dementia risk score for individuals to assess spatial variation of dementia risk, identify significant clusters (hotspots), and explore their association with socioeconomic status. We used clinical records from 16 general practices (468 Statistical Area level 1 s, N = 14,746) from the city of west Adelaide, Australia for the duration of 1 January 2012 to 31 December 2014...
November 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29122977/a%C3%AE-inhibits-srebp-2-activation-through-akt-inhibition
#12
Amany Mohamed, Anissa Viveiros, Kathleen Williams, Elena Posse de Chaves
We previously demonstrated that oligomeric Aβ42 (oAβ42 ) inhibits the mevalonate pathway impairing cholesterol synthesis and protein prenylation. Enzymes of the mevalonate pathway are regulated by the transcription factor sterol regulatory element binding protein (SREBP) 2. Here, we show that in several neuronal types challenged with o Aβ42, SREBP-2 activation is reduced. Moreover, SREBP-2 activation is also decreased in brain cortex of the Alzheimer's disease (AD) mouse model TgCRND8, suggesting that SREBP-2 may be affected in vivo during disease...
November 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29116115/characterization-of-apoj-reconstituted-high-density-lipoprotein-rhdl-nanodisc-for-the-potential-treatment-of-cerebral-%C3%AE-amyloidosis
#13
Sofía Fernández-de-Retana, Mary Cano-Sarabia, Paula Marazuela, Jose Luis Sánchez-Quesada, Annabel Garcia-Leon, Alex Montañola, Joan Montaner, Daniel Maspoch, Mar Hernández-Guillamon
Cerebral β-amyloidosis is a major feature of Alzheimer's disease (AD), characterized by the accumulation of β-amyloid protein (Aβ) in the brain. Several studies have implicated lipid/lipoprotein metabolism in the regulation of β-amyloidosis. In this regard, HDL (High Density Lipoprotein)-based therapies could ameliorate pathological features associated with AD. As apolipoprotein J (ApoJ) is a natural chaperone that interacts with Aβ, avoiding its aggregation and toxicity, in this study we propose to prepare reconstituted rHDL-rApoJ nanoparticles by assembling phospholipids with recombinant human ApoJ (rApoJ)...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115990/dhcr24-exerts-neuroprotection-upon-inflammation-induced-neuronal-death
#14
Henna Martiskainen, Kaisa M A Paldanius, Teemu Natunen, Mari Takalo, Mikael Marttinen, Stina Leskelä, Nadine Huber, Petra Mäkinen, Enni Bertling, Hiramani Dhungana, Mikko Huuskonen, Paavo Honkakoski, Pirta Hotulainen, Kirsi Rilla, Jari Koistinaho, Hilkka Soininen, Tarja Malm, Annakaisa Haapasalo, Mikko Hiltunen
BACKGROUND: DHCR24, involved in the de novo synthesis of cholesterol and protection of neuronal cells against different stress conditions, has been shown to be selectively downregulated in neurons of the affected brain areas in Alzheimer's disease. METHODS: Here, we investigated whether the overexpression of DHCR24 protects neurons against inflammation-induced neuronal death using co-cultures of mouse embryonic primary cortical neurons and BV2 microglial cells upon acute neuroinflammation...
November 7, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29111006/a-complex-association-between-abca7-genotypes-and-blood-lipid-levels-in-southern-chinese-han-patients-of-sporadic-alzheimer-s-disease
#15
Hui Li, Jinxia Zhou, Zongwei Yue, Li Feng, Zhaohui Luo, Si Chen, Xiaosu Yang, Bo Xiao
Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive cognitive decline. It can be divided into familial AD (FAD) and sporadic AD (SAD) based on the family history. Recently dysregulation of cholesterol homeostasis has been implicated in the development of late-onset AD. ATP-binding cassette transporter A7 (ABCA7) gene, regulating the transport of cholesterol, has been recently identified as a susceptible gene of AD by several large genome-wide association studies...
November 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29077483/risk-of-late-onset-alzheimer-s-disease-by-plasma-cholesterol-rational-in-silico-drug-investigation-of-pyrrole-based-hmg-coa-reductase-inhibitors
#16
Sajad Shahbazi, Jagdeep Kaur, Ananya Kuanar, Dattatreya Kar, Shikha Singh, Ranbir Chander Sobti
Alzheimer's disease (AD), a worldwide renowned progressive neurodegenerative disorder, is the most common cause of dementia. There are several studies on the important role of cholesterol metabolism in AD pathogenesis, which indicated that the high concentrations of serum cholesterol increase the risk of AD. Biosynthesis of the plasma cholesterol and other isoprenoids is catalyzed by 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) through the conversion of HMG-CoA to mevalonic acid in mevalonate pathway. Normally, the high level of plasma cholesterol is downregulated by HGMCR inhibition as the result of degradation of LDL, but in abnormal conditions, for example, high blood glucose, the HMGCR over activated resulting in uncontrolled blood cholesterol...
October 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/29066835/cellular-hormetic-response-to-27-hydroxycholesterol-promotes-neuroprotection-through-aicd-induction-of-mast4-abundance-and-kinase-activity
#17
Brendan Gongol, Traci L Marin, John D Jeppson, Karina Mayagoitia, Samuel Shin, Nicholas Sanchez, Wolff M Kirsch, Harry V Vinters, Christopher G Wilson, Othman Ghribi, Salvador Soriano
The function of the amyloid precursor protein (APP) in brain health remains unclear. This study elucidated a novel cytoprotective signaling pathway initiated by the APP transcriptionally active intracellular domain (AICD) in response to 27-hydroxycholesterol (27OHC), an oxidized cholesterol metabolite associated with neurodegeneration. The cellular response to 27OHC was hormetic, such that low, but not high, doses promoted AICD transactivation of microtubule associated serine/threonine kinase family member 4 (MAST4)...
October 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29065835/hydroxypropyl-%C3%AE-cyclodextrin-formulated-in-nasal-chitosan-microspheres-as-candidate-therapeutic-agent-in-alzheimer-s-disease
#18
Giovanna Rassu, Elisabetta Gavini, Antonio Carta, Antonella Obinu, Elena Piera Porcu, Paolo Giunchedi
Hydroxypropyl-β-cyclodextrin (HP-CD) is a hydroxyalkyl derivative of native β-cyclodextrin, cyclic oligosaccharide able to form inclusion complexes with many drugs and biomolecules [1]. Cyclodextrins have a possible neuroprotective effect due to their capability to extract and deplete cholesterol from cell membranes [1]. HP-CD is classified as an excipient (cyclodextrins are in fact widely used to improve solubility of poorly water soluble drugs) and it is not been FDA-approved as therapeutic agent. However HP-CD received the "orphan drug designation" in the United States and Europe because it is employed in individual compassionate use for patients suffering from Niemann-Pick type C...
October 19, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/29052144/the-effects-of-extracellular-serum-concentration-on-app-processing-in-npc1-deficient-app-overexpressing-n2a-cells
#19
M Maulik, D Vergote, G Phukan, J Chung, G Thinakaran, S Kar
Amyloid precursor protein (APP) is cleaved by a set of proteases including α-/β-/γ- and recently identified η-secretases, generating C-terminal fragments (CTFs) of varying lengths and amyloid β (Aβ) peptides, which are considered to play a pivotal role in Alzheimer's disease (AD) pathogenesis. Cellular cholesterol content/distribution can regulate the production/clearance of APP metabolites and hence modify AD pathology. To determine the functional relation between endosomal-lysosomal (EL) cholesterol sequestration and APP metabolism, we used our recently developed mouse N2a-ANPC cells that overexpress Swedish mutant human APP in the absence of cholesterol-trafficking Niemann-Pick type C1 (Npc1) protein...
October 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28987514/analysis-of-ptprk-polymorphisms-in-association-with-risk-and-age-at-onset-of-alzheimer-s-disease-cancer-risk-and-cholesterol
#20
Yang Chen, Chun Xu, Sam Harirforoosh, Xingguang Luo, Ke-Sheng Wang
The human receptor-type protein-tyrosine phosphatase kappa (PTPRK) gene is highly expressed in human brain and was previously associated with an increased risk of neuropsychiatric disorders and cancer. This study investigated the association of 52 single nucleotide polymorphisms (SNPs) in PTPRK with the risk and age at onset (AAO) of Alzheimer's disease (AD) in 791 AD patients and 782 controls. Our data analysis showed that five SNPs (top SNP rs4895829 with p = 0.0125) were associated with the risk of AD based on a multiple logistic regression (p < 0...
September 27, 2017: Journal of Psychiatric Research
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