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Alzheimers and cholesterol

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https://www.readbyqxmd.com/read/28444230/apoe-%C3%AE%C2%B54-%C3%AE%C2%B54-diminishes-neurotrophic-function-of-human-ipsc-derived-astrocytes
#1
Jing Zhao, Mary D Davis, Yuka Atagi, Mitsuru Shinohara, Neill R Graff-Radford, Steven G Younkin, Zbigniew K Wszolek, Takahisa Kanekiyo, Guojun Bu
The ε4 allele of the APOE gene encoding apolipoprotein E (apoE) is a strong genetic risk factor for aging-related cognitive decline as well as late-onset Alzheimer's disease (AD) compared to the common ε3 allele. In the central nervous system, apoE is produced primarily by astrocytes and functions in transporting lipids including cholesterol to support neuronal homeostasis and synaptic integrity. Although mouse models and corresponding primary cells have provided valuable tools for studying apoE isoform-dependent functions, recent studies have shown that human astrocytes have distinct gene expression profile compare with rodent astrocytes...
April 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28439555/structural-and-biochemical-differences-between-the-notch-and-the-amyloid-precursor-protein-transmembrane-domains
#2
Catherine L Deatherage, Zhenwei Lu, Brett M Kroncke, Sirui Ma, Jarrod A Smith, Markus W Voehler, Robert L McFeeters, Charles R Sanders
γ-Secretase cleavage of the Notch receptor transmembrane domain is a critical signaling event for various cellular processes. Efforts to develop inhibitors of γ-secretase cleavage of the amyloid-β precursor C99 protein as potential Alzheimer's disease therapeutics have been confounded by toxicity resulting from the inhibition of normal cleavage of Notch. We present biochemical and structural data for the combined transmembrane and juxtamembrane Notch domains (Notch-TMD) that illuminate Notch signaling and that can be compared and contrasted with the corresponding traits of C99...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28438747/low-ldl-cholesterol-pcsk9-and-hmgcr-genetic-variation-and-risk-of-alzheimer-s-disease-and-parkinson-s-disease-mendelian-randomisation-study
#3
Marianne Benn, Børge G Nordestgaard, Ruth Frikke-Schmidt, Anne Tybjærg-Hansen
Objective To test the hypothesis that low density lipoprotein (LDL) cholesterol due to genetic variation in the genes responsible for LDL cholesterol metabolism and biosynthesis(PCSK9 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), respectively) is associated with a high risk of Alzheimer's disease, vascular dementia, any dementia, and Parkinson's disease in the general population.Design Mendelian randomisation study.Setting Copenhagen General Population Study and Copenhagen City Heart Study.Participants 111 194 individuals from the Danish general population...
April 24, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28421328/association-of-adiponectin-leptin-and-resistin-with-inflammatory-markers-and-obesity-in-dementia
#4
Małgorzata Bednarska-Makaruk, Ałła Graban, Anna Wiśniewska, Wanda Łojkowska, Anna Bochyńska, Magdalena Gugała-Iwaniuk, Ksenia Sławińska, Agnieszka Ługowska, Danuta Ryglewicz, Hanna Wehr
The aim of the study was to determine the role of adiponectin, leptin and resistin in various types of dementia and to investigate their association with inflammatory markers, insulin resistance and abdominal obesity. In 205 patients with dementia [89 with Alzheimer's disease (AD), 47 with vascular dementia (VaD), 69 with mixed dementia (MD)], 113 persons with mild cognitive impairment and in 107 controls serum adiponectin, leptin and resistin levels, pro-inflammatory [interleukin-6 (IL-6), C-reactive protein (hsCRP) and chitotriosidase] and anti-inflammatory (25-OH vitamin D, HDL-cholesterol and paraoxonase 1) markers, as well as glucose metabolism parameters (glucose, insulin and HOMA-IR) were determined...
April 18, 2017: Biogerontology
https://www.readbyqxmd.com/read/28417263/rosuvastatin-attenuates-high-salt-and-cholesterol-diet-induced-neuroinflammation-and-cognitive-impairment-via-preventing-nuclear-factor-kappab-pathway
#5
Ibraheem Husain, Mohd Akhtar, Divya Vohora, Malik Zainul Abdin, Mohammad Islamuddin, Mohd Jawaid Akhtar, Abul Kalam Najmi
Recent attention is focused on the impact of diet on health and mental well-being. High-salt and cholesterol diet (HSCD) is known to be associated with neuroinflammation which is the predominant factor for neurodegenerative disease like Alzheimer disease (AD). In the present study, we examined the neuroprotective potential of rosuvastatin, an HMG-CoA reductase inhibitor against HSCD induced neuroinflammation and cognitive impairment. Our results demonstrated that HSCD-induced cognitive impairment as determined by Morris water maze (MWM) task...
April 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28413178/synthesized-a%C3%AE-42-caused-intracellular-oxidative-damage-leading-to-cell-death-via-lysosome-rupture
#6
Yuki Oku, Kazuma Murakami, Kazuhiro Irie, Jun Hoseki, Yasuyoshi Sakai
Neuronal cellular accumulation of amyloid beta peptide (Aβ) has been implicated in the pathogenesis of Alzheimer’s disease (AD). Intracellular accumulation of Aβ42, a toxic form of Aβ, was observed as an early event in AD patients. However, its contribution and the cellular mechanism of cell death remained unclear. We herein revealed the mechanism by which Aβ42 incorporated into cells leads to cell death by using chemically synthesized Aβ42 variants. The Aβ42 variant Aβ42 (E22P) which has an increased tendency to oligomerize, accumulated in lysosomes at an earlier stage than wild-type Aβ42, leading to higher ROS production and lysosomal membrane oxidation, and resulting in cell death...
April 12, 2017: Cell Structure and Function
https://www.readbyqxmd.com/read/28408965/phospholipase-c-related-catalytically-inactive-protein-can-regulate-obesity-a-state-of-peripheral-inflammation
#7
REVIEW
Yosuke Yamawaki, Kana Oue, Satomi Shirawachi, Satoshi Asano, Kae Harada, Takashi Kanematsu
Obesity is defined as abnormal or excessive fat accumulation. Chronic inflammation in fat influences the development of obesity-related diseases. Many reports state that obesity increases the risk of morbidity in many diseases, including hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, sleep apnea, and breast, prostate and colon cancers, leading to increased mortality. Obesity is also associated with chronic neuropathologic conditions such as depression and Alzheimer's disease. However, there is strong evidence that weight loss reduces these risks, by limiting blood pressure and improving levels of serum triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol...
February 2017: Japanese Dental Science Review
https://www.readbyqxmd.com/read/28399252/association-between-midlife-vascular-risk-factors-and-estimated-brain-amyloid-deposition
#8
Rebecca F Gottesman, Andrea L C Schneider, Yun Zhou, Josef Coresh, Edward Green, Naresh Gupta, David S Knopman, Akiva Mintz, Arman Rahmim, A Richey Sharrett, Lynne E Wagenknecht, Dean F Wong, Thomas H Mosley
Importance: Midlife vascular risk factors have been associated with late-life dementia. Whether these risk factors directly contribute to brain amyloid deposition is less well understood. Objective: To determine if midlife vascular risk factors are associated with late-life brain amyloid deposition, measured using florbetapir positron emission tomography (PET). Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC)-PET Amyloid Imaging Study, a prospective cohort study among 346 participants without dementia in 3 US communities (Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi) who have been evaluated for vascular risk factors and markers since 1987-1989 with florbetapir PET scans in 2011-2013...
April 11, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28384414/alteration-of-high-density-lipoproteins-functionality-in-alzheimer-s-disease-patients
#9
Pamela Camponova, Aurélie Le Page, Hicham Berrougui, Julie Lamoureux, Graham Pawelec, Jacek Witkowski, Tamas Fulop, Abdelouahed Khalil
The aims of the present study were to determine whether High-Density Lipoproteins functionality (HDL)-mediated cholesterol efflux is altered in Alzheimer's disease (AD) and to investigate the role and effect of amyloid-beta (Aβ) in the regulation of the anti-atherogenic activity of HDL. Eighty-seven elderly subjects were recruited, of whom 27 were healthy, 27 had mild cognitive impairment (MCI), and 33 had mild Alzheimer's disease (mAD). Our results showed that total cholesterol levels are negatively correlated with the Mini Mental State Examination (MMSE) score (r = -0...
April 6, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28373057/lysophosphatidylcholine-export-by-human-abca7
#10
Maiko Tomioka, Yoshinobu Toda, Noralyn B Mañucat, Hiroyasu Akatsu, Manabu Fukumoto, Nozomu Kono, Hiroyuki Arai, Noriyuki Kioka, Kazumitsu Ueda
The ATP-binding cassette transporter A7 (ABCA7), which is highly expressed in the brain, is associated with the pathogenesis of Alzheimer's disease (AD). However, the physiological function of ABCA7 and its transport substrates remain unclear. Immunohistochemical analyses of human brain sections from AD and non-AD subjects revealed that ABCA7 is expressed in neuron and microglia cells in the cerebral cortex. The transport substrates and acceptors were identified in BHK/ABCA7 cells and compared with those of ABCA1...
March 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28366823/redox-status-of-serum-apolipoprotein-e-and-its-impact-on-hdl-cholesterol-levels
#11
Kazuyoshi Yamauchi, Yuka Ebihara, Yasushi Kawakami
BACKGROUND: Apolipoprotein E (apoE) is closely involved in the pathogenesis of apoE-related diseases, such as Alzheimer's disease and cardiovascular disease. The redox modulation of cysteine-thiols in a protein is involved in various pathophysiological regulations; however, that of apoE has not been studied in detail. Herein, we devised an analytical method to determine the redox status of serum apoE and assessed its relation to serum cholesterol levels and apoE phenotype. METHODS: The present method was based on a band shift assay, using a photocleavable maleimide-conjugated polyethylene glycol...
March 30, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28350817/differential-associations-of-plasma-lipids-with-incident-dementia-and-dementia-subtypes-in-the-3c-study-a-longitudinal-population-based-prospective-cohort-study
#12
Sabrina Schilling, Christophe Tzourio, Aïcha Soumaré, Sara Kaffashian, Jean-François Dartigues, Marie-Laure Ancelin, Cécilia Samieri, Carole Dufouil, Stéphanie Debette
BACKGROUND: Vascular risk factors have been proposed as important targets for the prevention of dementia. As lipid fractions represent easily modifiable targets, we examined the longitudinal relationship of baseline lipid fractions with 13-y incident dementia and its subtypes (Alzheimer disease [AD] and mixed or vascular dementia) in older community-dwelling persons. METHODS AND FINDINGS: Non-institutionalized persons aged 65+ y (n = 9,294) were recruited for the Three-City Study (3C Study), a population-based cohort study from the electoral rolls of the cities of Dijon, Bordeaux, and Montpellier, France, between March 1999 and March 2001...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28340945/plasma-levels-of-apolipoprotein-e-apoe-genotype-and-risk-of-dementia-and-ischemic-heart-disease-a-review
#13
REVIEW
Katrine Laura Rasmussen
Dementia is one of the major causes of disability in later life, and ischemic heart disease is a leading cause of morbidity and mortality. Apolipoprotein E (apoE) plays a pivotal role in lipoprotein metabolism in the brain and in the periphery, and is implicated in both dementia and ischemic heart disease. Peripherally, liver-derived apoE is the main source of plasma apoE. Approximately half of plasma apoE is associated with triglyceride-rich lipoproteins, where apoE serves as the main ligand for the low density lipoprotein (LDL) receptor and the LDL receptor Related Protein (LRP)...
December 2016: Atherosclerosis
https://www.readbyqxmd.com/read/28315462/implications-of-cerebrovascular-atp-binding-cassette-transporter-g1-abcg1-and-apolipoprotein-m-in-cholesterol-transport-at-the-blood-brain-barrier
#14
Alexandra Carmen Kober, Anil Paul Chirackal Manavalan, Carmen Tam-Amersdorfer, Andreas Holmér, Ahmed Saeed, Elham Fanaee-Danesh, Martina Zandl, Nicole Maria Albrecher, Ingemar Björkhem, Gerhard M Kostner, Björn Dahlbäck, Ute Panzenboeck
Impaired cholesterol/lipoprotein metabolism is linked to neurodegenerative diseases such as Alzheimer's disease (AD). Cerebral cholesterol homeostasis is maintained by the highly efficient blood-brain barrier (BBB) and flux of the oxysterols 24(S)-hydroxycholesterol and 27-hydroxycholesterol, potent liver-X-receptor (LXR) activators. HDL and their apolipoproteins are crucial for cerebral lipid transfer, and loss of ATP binding cassette transporters (ABC)G1 and G4 results in toxic accumulation of oxysterols in the brain...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28304309/mouse-models-of-alzheimer-s-disease
#15
Gisela Esquerda-Canals, Laia Montoliu-Gaya, Jofre Güell-Bosch, Sandra Villegas
Alzheimer's disease (AD) is a neurodegenerative disorder that nowadays affects more than 40 million people worldwide and it is predicted to exponentially increase in the coming decades. Because no curative treatment exists, research on the pathophysiology of the disease, as well as the testing of new drugs, are mandatory. For these purposes, animal models constitute a valuable, although perfectible tool. This review takes a tour through several aspects of mouse models of AD, such as the generation of transgenic models, the relevance of the promoter driving the expression of the transgenes, and the concrete transgenes used to simulate AD pathophysiology...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28298292/cellular-cholesterol-homeostasis-in-alzheimer-s-disease
#16
Ta Yuan Chang, Yoshio Yamauchi, Mazahir Hasan, Catherine Cy Chang
Alzheimer's disease [AD] is the most common form of dementia in older adults. Currently, there is no cure for AD. The hallmark of AD is the accumulation of extracellular amyloid plaques composed of amyloid beta peptides [Abeta; especially Abeta1-42], and neurofibrillary tangles, composed of hyper-phosphorylated tau, accompanied with chronic neuroinflammation. Abeta are derived from the amyloid precursor protein APP. The oligomeric form of Abeta is probably the most neurotoxic species; its accumulation eventually forms the insoluble and aggregated amyloid plaques...
March 15, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28292942/the-apoe-receptors-vldlr-and-apoer2-in-central-nervous-system-function-and-disease
#17
Courtney Lane-Donovan, Joachim Herz
The low-density lipoprotein receptor (LDLR) family has long been studied for its role in cholesterol transport and metabolism; however, the identification of apolipoprotein E4 (ApoE4), an LDLR ligand, as a genetic risk factor for late-onset Alzheimers disease (AD) has focused attention on the role this receptor family plays in the central nervous system (CNS). Surprisingly, it was discovered that two LDLR family members, Apolipoprotein E receptor 2 (Apoer2) and very-low-density lipoprotein receptor (Vldlr), play key roles in brain development and adult synaptic plasticity, primarily by mediating Reelin signaling...
March 14, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28290249/in-vitro-and-in-silico-studies-of-mangiferin-from-aphloia-theiformis-on-key-enzymes-linked-to-diabetes-type-2-and-associated-complications
#18
Marie C N Picot, Gokhan Zengin, Adriano Mollica, Azzurra Stefanucci, Simone Carradori, Mohamad F Mahomoodally
BACKGROUND: Mangiferin, was identified in the crude methanol extract, ethyl acetate, and n-butanol fractions of Aphloia theiformis (Vahl.) Benn. OBJECTIVE: To study the plausible binding modes of mangiferin to key enzymes linked to diabetes type 2 (DT2), obesity, hypertension, Alzheimer's disease, and urolithiasis using molecular docking. METHOD: Crystallographic structures of α-amylase, α-glucosidase, glycogen phosphorylase (GP), pancreatic lipase, cholesterol esterase (CEase), angiotensin-I-converting enzyme (ACE), acetyl cholinesterase (AChE), and urease available on the Protein Databank database were docked to mangiferin using Gold 6...
March 7, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28275046/self-reported-sleep-disturbance-and-incidence-of-dementia-in-ageing-men
#19
Maria K Luojus, Soili M Lehto, Tommi Tolmunen, Anna-Katharine Brem, Eija Lönnroos, Jussi Kauhanen
BACKGROUND: Sleep disturbance is suggested to contribute to the development of dementia. However, prospective longitudinal data from middle-aged populations are scarce. METHODS: We investigated a population-based sample of 2386 men aged 42-62 years at baseline during 1984-1989. Participants having a history of mental illnesses, psychiatric medication, Parkinson's disease or dementia within 2 years after baseline (n=296) were excluded. Difficulty falling asleep or maintaining sleep, sleep duration and daytime tiredness were enquired...
April 2017: Journal of Epidemiology and Community Health
https://www.readbyqxmd.com/read/28274859/longitudinal-lipid-profile-variations-and-clinical-change-in-alzheimer-s-disease-dementia
#20
Fabricio Ferreira de Oliveira, Elizabeth Suchi Chen, Marilia Cardoso Smith, Paulo Henrique Ferreira Bertolucci
Hypercholesterolemia and statin use have been unevenly associated with clinical change in Alzheimer's disease dementia. In this longitudinal study, 192 consecutive outpatients with late-onset Alzheimer's disease dementia were stratified according to APOE haplotypes, and followed for one year to investigate associations of lipid profile variations and lipophilic statin therapy with changes in cognition, caregiver burden, basic and instrumental functionality. Overall, 102 patients (53.1%) carried APOE4+ haplotypes and 90 (46...
April 12, 2017: Neuroscience Letters
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