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Alzheimers and cholesterol

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https://www.readbyqxmd.com/read/27911324/proteomics-analysis-of-blood-serums-from-alzheimer-s-disease-patients-using-itraq-labeling-technology
#1
Liming Shen, Liping Liao, Cheng Chen, Yi Guo, Dalin Song, Yong Wang, Youjiao Chen, Kaoyuan Zhang, Ming Ying, Shuiming Li, Qiong Liu, Jiazuan Ni
Alzheimer' disease (AD) is the most common form of dementia affecting up to 6% of the population over the age of 65. In order to discover differentially expressed proteins that might serve as potential biomarkers, the serums from AD patients and healthy controls were compared and analyzed using the proteomics approach of isobaric tagging for relative and absolute quantitation (iTRAQ). For the first time, AD biomarkers in serums are investigated in the Han Chinese population using iTRAQ labeled proteomics strategy...
December 1, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911314/updating-the-evidence-on-the-association-between-serum-cholesterol-and-risk-of%C3%A2-late-life-dementia-review-and%C3%A2-meta-analysis
#2
Kaarin J Anstey, Kimberly Ashby-Mitchell, Ruth Peters
BACKGROUND: Cohort studies have reported that midlife high total serum cholesterol (TC) is associated with increased risk of Alzheimer's disease (AD) in late-life but findings have been based on few studies and previous reviews have been limited by a lack of compatible data. OBJECTIVE: We synthesized all high quality data from cohort studies reporting on the association between total serum cholesterol measured and late-life cognitive outcomes including Alzheimer's disease (AD), vascular dementia (VaD), any dementia, mild cognitive impairment (MCI), and cognitive decline...
November 29, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911307/a-high-cholesterol-diet-increases-27-hydroxycholesterol-and-modifies-estrogen-receptor-expression-and-neurodegeneration-in-rabbit-hippocampus
#3
Sylwia W Brooks, Ava C Dykes, Bernard G Schreurs
Hypercholesterolemia has been implicated in numerous health problems from cardiovascular disease to neurodegeneration. High serum cholesterol levels in midlife have been associated with an increased risk of developing Alzheimer's disease (AD) later in life which suggests that the pathways leading to AD pathology might be activated decades before the symptoms of the disease are detected. Cholesterol-fed animals, particularly cholesterol-fed rabbits, exhibit brain pathology similar to the changes found in brains of AD patients...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27902765/loss-of-cathepsin-b-and-l-leads-to-lysosomal-dysfunction-npc-like-cholesterol-sequestration-and-accumulation-of-the-key-alzheimer-s-proteins
#4
Stjepko Cermak, Marko Kosicek, Aleksandra Mladenovic-Djordjevic, Kosara Smiljanic, Selma Kanazir, Silva Hecimovic
Proper function of lysosomes is particularly important in neurons, as they cannot dilute accumulated toxic molecules and aggregates by cell division. Thus, impairment of lysosomal function plays an important role in neuronal degeneration and in the pathogenesis of numerous neurodegenerative diseases. In this work we analyzed how inhibition and/or loss of the major lysosomal proteases, the cysteine cathepsins B and L (CtsB/L), affects lysosomal function, cholesterol metabolism and degradation of the key Alzheimer's disease (AD) proteins...
2016: PloS One
https://www.readbyqxmd.com/read/27889409/bioactive-compound-screen-for-pharmacological-enhancers-of-apolipoprotein-e-in-primary-human-astrocytes
#5
Gina M Finan, Ronald Realubit, Sungkwon Chung, Dieter Lütjohann, Nan Wang, John R Cirrito, Charles Karan, Tae-Wan Kim
Pharmacological screening in physiologically relevant brain cells is crucial for identifying neuroactive compounds that better translate into in vivo biology and efficacious therapeutics. Pharmacological enhancement of apolipoprotein E (apoE), a cholesterol-transporting apolipoprotein, has been proposed as a promising therapeutic approach for Alzheimer's disease. Several nuclear receptor agonists were initially shown to increase brain apoE levels together with ATP-binding cassette transporter 1 (ABCA1), but their underlying mechanisms remain unclear...
November 18, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27884599/influence-of-sequence-and-lipid-type-on-membrane-perturbation-by-human-and-rat-amyloid-%C3%AE-peptide-1-42
#6
Anne M Brown, David R Bevan
The hallmark characteristics of plaque formation and neuronal cell death in Alzheimer's disease (AD) are caused principally by the amyloid β-peptide (Aβ). Aβ sequence and lipid composition are essential variables to consider when elucidating the impact of biological membranes on Aβ structure and the effect of Aβ on membrane integrity. Atomistic molecular dynamics simulations testing two Aβ sequences, human and rat Aβ (HAβ and RAβ, respectively), and five lipid types were performed to assess the effect of these variables on membrane perturbation and potential link to AD phenotype differences based on differences in sequence...
November 21, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27836779/contribution-of-cholesterol-and-oxysterols-to-the-pathophysiology-of-parkinson-s-disease
#7
REVIEW
Margaux Doria, Lucie Maugest, Thibault Moreau, Gérard Lizard, Anne Vejux
Neurodegenerative diseases are a major public health issue worldwide. Some countries, including France, have engaged in research into the causes of Parkinson's disease, Alzheimer's disease, and multiple sclerosis and the management of these patients. It should lead to a better understanding of the mechanisms leading to these diseases including the possible involvement of lipids in their pathogenesis. Parkinson's disease is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein (Lewy bodies)...
November 9, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27824936/differential-effects-of-apoe4-and-activation-of-abca1-on-brain-and-plasma-lipoproteins
#8
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/27823753/alzheimer-s-disease-apolipoprotein-e-and-hormone-replacement-therapy
#9
REVIEW
H Depypere, A Vierin, S Weyers, A Sieben
Alzheimer's disease is the most frequent cause of dementia in older patients. The prevalence is higher in women than in men. This may be the result of both the higher life expectancy of women and the loss of neuroprotective estrogen after menopause. Earlier age at menopause (spontaneous or surgical) is associated with an enhanced risk of developing Alzheimer's disease. Therefore, it is postulated that estrogen could be protective against it. If so, increasing exposure to estrogen through the use of postmenopausal hormone replacement could also be protective against Alzheimer's disease...
December 2016: Maturitas
https://www.readbyqxmd.com/read/27802238/homocysteine-and-real-space-navigation-performance-among-non-demented-older-adults
#10
Martina Paĭízková, Ross Andel, Ondĭej Lerch, Hana Marková, Ivana Gažová, Martin Vyhnálek, Jakub Hort, Jan Laczó
BACKGROUND: High plasma homocysteine (Hcy) level is related to higher risk of Alzheimer's disease (AD) and lower cognitive performance in older adults. OBJECTIVE: To assess the association between plasma Hcy level and real-space navigation performance and the role of vascular risk and protective factors, APOE status, and white matter lesions (WML) on this association. METHODS: Ninety-two non-demented older adults (29 with amnestic mild cognitive impairment, 46 with subjective cognitive decline, and 17 cognitively normal older adults) underwent spatial navigation testing of egocentric, allocentric, and mixed navigation in a real-space analogue of the Morris water maze, neuropsychological examination, blood collection, and MRI brain scan with evaluation of WML...
October 11, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27801864/tocotrienol-affects-oxidative-stress-cholesterol-homeostasis-and-the-amyloidogenic-pathway-in-neuroblastoma-cells-consequences-for-alzheimer-s-disease
#11
Marcus O W Grimm, Liesa Regner, Janine Mett, Christoph P Stahlmann, Pascal Schorr, Christopher Nelke, Olga Streidenberger, Hannah Stoetzel, Jakob Winkler, Shatha R Zaidan, Andrea Thiel, Kristina Endres, Heike S Grimm, Dietrich A Volmer, Tobias Hartmann
One of the characteristics of Alzheimer´s disease (AD) is an increased amyloid load and an enhanced level of reactive oxidative species (ROS). Vitamin E has known beneficial neuroprotective effects, and previously, some studies suggested that vitamin E is associated with a reduced risk of AD due to its antioxidative properties. However, epidemiological studies and nutritional approaches of vitamin E treatment are controversial. Here, we investigate the effect of α-tocotrienol, which belongs to the group of vitamin E, on AD-relevant processes in neuronal cell lines...
October 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27792010/theobromine-induced-changes-in-a1-purinergic-receptor-gene-expression-and-distribution-in-a-rat-brain-alzheimer-s-disease-model
#12
Jesus Mendiola-Precoma, Karla Padilla, Alfredo Rodríguez-Cruz, Laura C Berumen, Ricardo Miledi, Guadalupe García-Alcocer
Dementia caused by Alzheimer's disease (AD) is mainly characterized by accumulation in the brain of extra- and intraneuronal amyloid-β (Aβ) and tau proteins, respectively, which selectively affect specific regions, particularly the neocortex and the hippocampus. Sporadic AD is mainly caused by an increase in apolipoprotein E, a component of chylomicrons, which are cholesterol transporters in the brain. Recent studies have shown that high lipid levels, especially cholesterol, are linked to AD. Adenosine is an atypical neurotransmitter that regulates a wide range of physiological functions by activating four P1 receptors (A1, A2A, A2B, and A3) and P2 purinergic receptors that are G protein-coupled...
October 24, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27784219/serum-starvation-induces-bace1-processing-and-secretion
#13
Alexandra-Vasiliki Stavropoulou, Olga Mavrofrydi, Paul Saftig, Spiros Efthimiopoulos
β-secretase (BACE1) is a type 1 transmembrane protein implicated in Alzheimer's Disease (AD) pathogenesis. Cleavage of Amyloid Precursor Protein (APP), initiated by BACE1 and followed by γ-secretase, leads to the formation of toxic Aβ peptides. Increased levels of BACE1 have been detected in the CSF of AD patients compared to age-matched healthy controls indicating that neurodegenerative conditions induce shedding of BACE1. To mimic such conditions, we examined whether serum deprivation stimulates proteolysis-dependent secretion of BACE1...
October 25, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27773727/integrated-late-onset-alzheimer-s-disease-load-susceptibility-genes-cholesterol-metabolism-and-trafficking-perspectives
#14
REVIEW
Hee Kim Dong, Jeong-An Gim, Seung Hyeon Yeo, Heui-Soo Kim
Late onset Alzheimer's disease (LOAD) is the most common type of dementia and is characterized by decreased amyloid-β (Aβ) clearance from the brain. Cholesterol regulates the production and clearance of Aβ. Genome-wide association study (GWAS) suggests that at least 20 genes are associated with LOAD. The genes APOE, CLU, SORL1, PICALM, and BIN1 have a relatively high LOAD susceptibility. Additional experimental and bioinformatic approaches to integrate data from genetics, epigenetics, and molecular networks may further increase our understanding of LOAD in relation to cholesterol metabolism and trafficking...
January 15, 2017: Gene
https://www.readbyqxmd.com/read/27768960/anomalies-occurring-in-lipid-profiles-and-protein-distribution-in-frontal-cortex-lipid-rafts-in-dementia-with-lewy-bodies-disclose-neurochemical-traits-partially-shared-by-alzheimer-s-and-parkinson-s-diseases
#15
Raquel Marin, Noemí Fabelo, Virginia Martín, Paula Garcia-Esparcia, Isidre Ferrer, David Quinto-Alemany, Mario Díaz
Lipid rafts are highly dynamic membrane microdomains intimately associated with cell signaling. Compelling evidence has demonstrated that alterations in lipid rafts are associated with neurodegenerative diseases such Alzheimer's disease, but at present, whether alterations in lipid raft microdomains occur in other types of dementia such dementia with Lewy bodies (DLB) remains unknown. Our analyses reveal that lipid rafts from DLB exhibit aberrant lipid profiles including low levels of n-3 long-chain polyunsaturated fatty acids (mainly docosahexaenoic acid), plasmalogens and cholesterol, and reduced unsaturation and peroxidability indexes...
September 6, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27757035/role-of-berberine-in-alzheimer-s-disease
#16
Zhiyou Cai, Chuanling Wang, Wenming Yang
Berberine, an important protoberberine isoquinoline alkaloid, has several pharmacological activities, including antimicrobial, glucose- and cholesterol-lowering, antitumoral, and immunomodulatory properties. Substantial studies suggest that berberine may be beneficial to Alzheimer's disease (AD) by limiting the pathogenesis of extracellular amyloid plaques and intracellular neurofibrillary tangles. Increasing evidence has indicated that berberine exerts a protective role in atherosclerosis related to lipid- and glucose-lowering properties, implicating that berberine has the potential to inhibit these risk factors for AD...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/27730513/middle-aged-diabetic-females-and-males-present-distinct-susceptibility-to-alzheimer-disease-like-pathology
#17
E Candeias, A I Duarte, I Sebastião, M A Fernandes, A I Plácido, C Carvalho, S Correia, R X Santos, R Seiça, M S Santos, C R Oliveira, P I Moreira
Type 2 diabetes (T2D) is a highly concerning public health problem of the twenty-first century. Currently, it is estimated that T2D affects 422 million people worldwide with a rapidly increasing prevalence. During the past two decades, T2D has been widely shown to have a major impact in the brain. This, together with the cognitive decline and increased risk for dementia upon T2D, may arise from the complex interaction between normal brain aging and central insulin signaling dysfunction. Among the several features shared between T2D and some neurodegenerative disorders (e...
October 11, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27727284/orthostatic-hypotension-and-the-long-term-risk-of-dementia-a-population-based-study
#18
Frank J Wolters, Francesco U S Mattace-Raso, Peter J Koudstaal, Albert Hofman, M Arfan Ikram
BACKGROUND: Orthostatic hypotension (OH) is a common cause of transient cerebral hypoperfusion in the population. Cerebral hypoperfusion is widely implicated in cognitive impairment, but whether OH contributes to cognitive decline and dementia is uncertain. We aimed to determine the association between OH and the risk of developing dementia in the general population. METHODS AND FINDINGS: Between 4 October 1989 and 17 June 1993, we assessed OH in non-demented, stroke-free participants of the population-based Rotterdam Study...
October 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27687218/changes-in-brain-oxysterols-at-different-stages-of-alzheimer-s-disease-their-involvement-in-neuroinflammation
#19
Gabriella Testa, Erica Staurenghi, Chiara Zerbinati, Simona Gargiulo, Luigi Iuliano, Giorgio Giaccone, Fausto Fantò, Giuseppe Poli, Gabriella Leonarduzzi, Paola Gamba
Alzheimer's disease (AD) is a gradually debilitating disease that leads to dementia. The molecular mechanisms underlying AD are still not clear, and at present no reliable biomarkers are available for the early diagnosis. In the last several years, together with oxidative stress and neuroinflammation, altered cholesterol metabolism in the brain has become increasingly implicated in AD progression. A significant body of evidence indicates that oxidized cholesterol, in the form of oxysterols, is one of the main triggers of AD...
September 16, 2016: Redox Biology
https://www.readbyqxmd.com/read/27663235/apolipoproteins-and-hdl-cholesterol-do-not-associate-with-the-risk-of-future-dementia-and-alzheimer-s-disease-the-national-finnish-population-study-finrisk
#20
Juho Tynkkynen, Jussi A Hernesniemi, Tiina Laatikainen, Aki S Havulinna, Jouko Sundvall, Jaana Leiviskä, Perttu Salo, Veikko Salomaa
Data on associations of apolipoproteins A-I and B (apo A-I, apo B) and HDL cholesterol (HDL-C) with dementia and Alzheimer's disease (AD) are conflicting. Our aim was to examine, whether apo B, apoA-I, their ratio, or HDL-C are significant, independent predictors of incident dementia and AD in the general population free of dementia at baseline. We analyzed the results from two Finnish prospective population-based cohort studies in a total of 13,275 subjects aged 25 to 74 years with mainly Caucasian ethnicity...
September 23, 2016: Age (2005-)
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