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Alzheimers and cholesterol

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https://www.readbyqxmd.com/read/29627763/-lipid-raft-aging-in-the-human-frontal-cortex-during-nonpathological-aging-gender-influences-and-potential-implications-in-alzheimer-s-disease
#1
Mario Díaz, Noemí Fabelo, Isidre Ferrer, Raquel Marín
Lipid rafts are highly dynamic membrane domains featured by distinctive biochemical composition and physicochemical properties compared with the surrounding plasma membrane. These microstructures are associated not only with cellular signaling and communication in normal nerve cells but also with pathological processing of amyloid precursor protein in Alzheimer's disease. Using lipid rafts isolated from human frontal cortex in nondemented subjects aging 24 to 85 years, we demonstrate here that lipid structure of lipid rafts undergo significant alterations of specific lipid classes and phospholipid-bound fatty acids as brain cortex correlating with aging...
March 10, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29625180/a%C3%AE-oligomer-uptake-and-the-resulting-inflammatory-response-in-adult-human-astrocytes-are-precluded-by-an-anti-a%C3%AE-single-chain-variable-fragment-in-combination-with-an-apoe-mimetic-peptide
#2
Laia Montoliu-Gaya, Sandra D Mulder, Maaike A C Herrebout, Johannes C Baayen, Sandra Villegas, Robert Veerhuis
An imbalance between production and clearance of soluble amyloid-β (Aβ) initiates the pathological process in sporadic Alzheimer's disease (AD). Aβ-specific antibodies seemed promising as therapeutic option in AD mouse models. In patients, however, vascular side-effects and Aβ-antibody complex-induced microglial and/or perivascular macrophage inflammatory responses were encountered. To prevent inflammatory reactions, we designed a single chain variable fragment (scFv-h3D6), based on monoclonal antibody bapineuzumab (mAb-h3D6), but lacking the Fc region...
April 3, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29623835/apoe4-may-be-a-promising-target-for-treatment-of-coronary-heart-disease-and-alzheimer-s-disease
#3
Wei Chen, Fengzhong Jin, Guihua Cao, Rong Mei, Yayun Wang, Pan Long, Xiaoming Wang, Wei Ge
Alzheimer disease (AD) is most common neurodegenerative disorder of dementia, as we all know, ApoE4 is the greatest genetic risk factor of late-onset Alzheimer's disease (LOAD). Coronary heart disease (CHD) lead to one-fourth of all deaths in industrialized countries, it is reported that ApoE4 increases the risk of coronary heart disease as well. Furthermore, evidence show that coronary heart disease also increases the incidence of Alzheimer's disease. Whether ApoE4 is a bridge connecting AD with CHD or not? And what are the special mechanism and therapeutic methods? Researchers found that cholesterol metabolic disorder is common causes and risk factors of AD and CHD...
April 5, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29610549/biochemical-properties-of-cholesterol-aldehyde-secosterol-and-its-derivatives
#4
REVIEW
Noriyuki Miyoshi
Elevated levels of cholesterol aldehyde, 3β-hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol-A, also called 5,6-secosterol), and its aldolization product (secosterol-B) have been detected in human atherosclerotic plaques and tissues samples of brains affected by neurodegeneration, such as Alzheimer's disease and Lewy body dementia suggesting that increased formation of these compounds may be associated with inflammation-related diseases. Secosterol-A and secosterol-B, and also further oxidized products seco-A-COOH and seco-B-COOH induce several pro-inflammatory activities in vitro ...
March 2018: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/29605487/association-between-abca1-gene-polymorphisms-and-the-therapeutic-response-to-donepezil-therapy-in-han-chinese-patients-with-alzheimer-s-disease
#5
Jin Lu, Jianliang Fu, Yuan Zhong, Quanjun Yang, Jinlu Huang, Jie Li, Yan Huo, Yuwu Zhao, Lili Wan, Cheng Guo
AIM: It is reported that ABCA1, which plays a key role in cholesterol transport and apolipoprotein E (APOE) metabolism in the brain, is related to Alzheimer's disease. However, few studies have focused on the relationship between the ABCA1 gene and the therapeutic response to donepezil (DNP), which has been shown to be related to reduced sAPP production.This study evaluated the association between the ABCA1 gene polymorphism and the clinical response to donepezil therapy in Han Chinese patients with Alzheimer's disease...
March 29, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29587752/alzheimer-like-brain-metabolic-and-structural-features-in-cholesterol-fed-rabbit-detected-by-magnetic-resonance-imaging
#6
Ping Jin, Yongming Pan, Zhiyong Pan, Jianqin Xu, Min Lin, Zhichao Sun, Minli Chen, Maosheng Xu
BACKGROUND: Hypercholesterolemia is known to increase the risk of AD in later life, the purpose of this study is to illustrate brain metabolic and structural changes in a cholesterol-fed rabbit model of Alzheimer's Disease (AD) by using clinical 3 T Magnetic Resonance Imaging (MRI). METHODS: The Institutional Animal Care and Use Committee of Zhejiang Chinese Medical University approved the study. Totally 16 Japanese White Rabbits (JWR) were randomly divided into 2 groups including normal control group fed with routine diet (group NC) and high cholesterol diet group (group CD) fed a 2% cholesterol diet with 0...
March 27, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29582495/targeting-alzheimer-s-disease-with-gene-and-cell-therapies
#7
REVIEW
Raúl Loera-Valencia, Antonio Piras, Muhammad Al Mustafa Ismail, Shaffi Manchanda, Helga Eyjolfsdottir, Takaomi C Saido, Jan Johansson, Maria Eriksdotter, Bengt Winblad, Per Nilsson
Alzheimer’ s disease (AD) causes dementia in both young and old people affecting more than 40 million people worldwide. The two neuropathological hallmarks of the disease, amyloid beta (Aβ) plaques and neurofibrillary tangles consisting of protein tau are considered the major contributors to the disease. However, a more complete picture reveals significant neurodegeneration and decreased cell survival, neuroinflammation, changes in protein homeostasis and alterations in lipid and cholesterol metabolism...
March 26, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29578488/risk-factors-associated-with-cortical-thickness-and-white-matter-hyperintensities-in-dementia-free-okinawan-elderly
#8
Lisa C Silbert, David Lahna, Nutta-On Promjunyakul, Erin Boespflug, Yusuke Ohya, Yasushi Higashiuesato, Junko Nishihira, Yuriko Katsumata, Takashi Tokashiki, Hiroko Dodge
BACKGROUND: Cortical gray matter (GM) and white matter (WM) deterioration are signals of neurodegeneration and increased dementia risk; however, their specific etiologies in dementia-free aging is unclear. OBJECTIVE: The objective of this study was to examine potentially modifiable risk factors of GM and WM degeneration in a well-characterized cohort of dementia-free elderly. METHODS: 96 Okinawan elderly participants (age 83.6) from the Keys to Optimal Cognitive Aging Project (KOCOA) underwent MRI and cognitive evaluation...
March 23, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29578354/considerations-on-accuracy-pattern-and-possible-underlying-factors-of-brain-microbleed-progression-in-older-adults-with-absence-or-mild-presence-of-vascular-pathology
#9
Alice M Harper, Lauren Clayson, Joanna M Wardlaw, Maria Del C Valdés Hernández
Objective To analyse brain microbleed (BMB) progression, its possible underlying factors, and the influence of inter-observer differences, in older individuals with none or mild vascular pathology. Methods This study analysed magnetic resonance images, cognitive, demographic and laboratory data from all individuals from the Alzheimer's Disease (AD) Neuroimaging Initiative database who had the required sequences for identifying BMBs over three consecutive years at the time the database was accessed (January 2016)...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29574441/lifestyle-and-vascular-risk-effects-on-mri-based-biomarkers-of-alzheimer-s-disease-a-cross-sectional-study-of-middle-aged-adults-from-the-broader-new-york-city-area
#10
Lisa Mosconi, Michelle Walters, Joanna Sterling, Crystal Quinn, Pauline McHugh, Randolph E Andrews, Dawn C Matthews, Christine Ganzer, Ricardo S Osorio, Richard S Isaacson, Mony J De Leon, Antonio Convit
OBJECTIVE: To investigate the effects of lifestyle and vascular-related risk factors for Alzheimer's disease (AD) on in vivo MRI-based brain atrophy in asymptomatic young to middle-aged adults. DESIGN: Cross-sectional, observational. SETTING: Broader New York City area. Two research centres affiliated with the Alzheimer's disease Core Center at New York University School of Medicine. PARTICIPANTS: We studied 116 cognitively normal healthy research participants aged 30-60 years, who completed a three-dimensional T1-weighted volumetric MRI and had lifestyle (diet, physical activity and intellectual enrichment), vascular risk (overweight, hypertension, insulin resistance, elevated cholesterol and homocysteine) and cognition (memory, executive function, language) data...
March 23, 2018: BMJ Open
https://www.readbyqxmd.com/read/29562810/loss-of-function-pcsk9-mutations-are-not-associated-with-alzheimer-disease
#11
Martine Paquette, Yascara Grisel Luna Saavedra, Judes Poirier, Louise Théroux, Doris Dea, Alexis Baass, Robert Dufour
BACKGROUND: Hypercholesterolemia is a major risk factor for the late-onset form of Alzheimer disease (AD). Loss-of-function (LOF) mutations of PCSK9 and PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and have been associated with a reduced risk of cardiovascular disease. The aim of this study was to examine the effect of PCSK9 LOF variants on risk and age of onset of AD. METHODS: A total of 878 participants (410 controls and 468 AD cases) from the Quebec Founder Population were included in the study...
January 1, 2018: Journal of Geriatric Psychiatry and Neurology
https://www.readbyqxmd.com/read/29559956/the-role-of-apoe-polymorphism-in-the-relationship-between-serum-steroid-hormone-levels-and-cognition-in-older-chinese-adults-a-cross-sectional-study
#12
Xiaochen Huang, Shengqi Dong, Jie Zhen, Huiqiang Zhang, Tong Lin, Yuhong Zeng, Nicholas Van Halm-Lutterodt, Linhong Yuan
Background: Epidemiology studies have indicated an association of apolipoprotein E (ApoE) genetic polymorphism and circulating steroid hormone levels with the risk of Alzheimer's disease. The established physiologic relationship between apolipoproteins and steroid hormone indicate an important role of ApoE polymorphism in impacting the relationship between serum steroid hormones and cognition in the elderly. Study design: A total of 500 Chinese adults aged between 50 and 75 participated in this community-based cross-sectional study...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29559905/molecular-mechanisms-for-herpes-simplex-virus-type-1-pathogenesis-in-alzheimer-s-disease
#13
REVIEW
Steven A Harris, Elizabeth A Harris
This review focuses on research in the areas of epidemiology, neuropathology, molecular biology and genetics that implicates herpes simplex virus type 1 (HSV-1) as a causative agent in the pathogenesis of sporadic Alzheimer's disease (AD). Molecular mechanisms whereby HSV-1 induces AD-related pathophysiology and pathology, including neuronal production and accumulation of amyloid beta (Aβ), hyperphosphorylation of tau proteins, dysregulation of calcium homeostasis, and impaired autophagy, are discussed. HSV-1 causes additional AD pathologies through mechanisms that promote neuroinflammation, oxidative stress, mitochondrial damage, synaptic dysfunction, and neuronal apoptosis...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29559883/estrogen-interactions-with-lipid-rafts-related-to-neuroprotection-impact-of-brain-ageing-and-menopause
#14
REVIEW
Raquel Marin, Mario Diaz
Estrogens (E2) exert a plethora of neuroprotective actions against aged-associated brain diseases, including Alzheimer's disease (AD). Part of these actions takes place through binding to estrogen receptors (ER) embedded in signalosomes, where numerous signaling proteins are clustered. Signalosomes are preferentially located in lipid rafts which are dynamic membrane microstructures characterized by a peculiar lipid composition enriched in gangliosides, saturated fatty acids, cholesterol, and sphingolipids. Rapid E2 interactions with ER-related signalosomes appear to trigger intracellular signaling ultimately leading to the activation of molecular mechanisms against AD...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29557360/neuroprotective-effects-of-statins-against-amyloid-%C3%AE-induced-neurotoxicity
#15
REVIEW
Hsin-Hua Li, Chih-Li Lin, Chien-Ning Huang
A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer's disease (AD). In particular, dysregulation of cholesterol homeostasis in the brain has been reported to considerably increase the risk of developing AD. Thus, dysregulation of lipid homeostasis may increase the amyloid β (Aβ) levels by affecting amyloid precursor protein (APP) cleavage, which is the most important risk factor involved in the pathogenesis of AD. Previous research demonstrated that Aβ can trigger neuronal insulin resistance, which plays an important role in response to Aβ-induced neurotoxicity in AD...
February 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29556189/royal-jelly-reduces-cholesterol-levels-ameliorates-a%C3%AE-pathology-and-enhances-neuronal-metabolic-activities-in-a-rabbit-model-of-alzheimer-s-disease
#16
Yongming Pan, Jianqin Xu, Cheng Chen, Fangming Chen, Ping Jin, Keyan Zhu, Chenyue W Hu, Mengmeng You, Minli Chen, Fuliang Hu
Alzheimer's disease (AD) is the most common form of dementia characterized by aggregation of amyloid β (Aβ) and neuronal loss. One of the risk factors for AD is high cholesterol levels, which are known to promote Aβ deposition. Previous studies have shown that royal jelly (RJ), a product of worker bees, has potential neuroprotective effects and can attenuate Aβ toxicity. However, little is known about how RJ regulates Aβ formation and its effects on cholesterol levels and neuronal metabolic activities...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29555421/neurodegenerative-diseases-infectious-pathologies-and-liquid-crystals-hypothesis-of-a-common-information-vector-involving-a-multidisciplinary-approach
#17
C Binot, C-H Chouard
The existence of an information vector common to very different pathologies is the hypothesis of one of us, the argumentation and discussion of which we present here. It is a mesomorphic state of material called liquid crystal. The liquid-ordered (Lo) phase, made up of membrane rafts mediated by cholesterol, lies at the center of our concept. This mesophase is either preexistent and then modified by the pathogenic process, or initiated by the latter. The most notable disorders involved are Alzheimer's, Parkinson's, Charcot and Creutzfeldt-Jakob diseases, flu-like illnesses and acquired immunodeficiency syndrome (AIDS), although this list may well be extended to include other anisotropic, birefringent amyloid proteinopathies, which have properties compatible with those of liquid crystals...
March 16, 2018: Revue Neurologique
https://www.readbyqxmd.com/read/29545167/vitexin-inhibits-a%C3%AE-25-35-induced-toxicity-in-neuro-2a-cells-by-augmenting-nrf-2-ho-1-dependent-antioxidant-pathway-and-regulating-lipid-homeostasis-by-the-activation-of-lxr-%C3%AE
#18
Dicson Sheeja Malar, Venkatesan Suryanarayanan, Mani Iyer Prasanth, Sanjeev Kumar Singh, Krishnaswamy Balamurugan, Kasi Pandima Devi
Amyloid beta (Aβ) formation is one of the neuropathological hallmarks of Alzheimer's disease (AD), which induces the generation of reactive oxygen species (ROS), further leading to the alteration of several signalling pathways. In the present study, vitexin has been evaluated for its neuroprotective activity against Aβ25-35 induced toxicity in Neuro-2a cells. Results of cell free studies indicated that vitexin significantly inhibited the aggregation of Aβ25-35 . Studies in Neuro-2a cells revealed that Aβ25-35 significantly affected the cell viability by inducing ROS mediated toxicity and apoptosis...
March 12, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29541536/reduced-vascular-risk-factors-in-parkinson-s-disease-dementia-and-dementia-with-lewy-bodies-compared-to-alzheimer-s-disease
#19
Po-Chi Chan, Cheng-Yu Wei, Guang-Uei Hung, Pai-Yi Chiu
Objectives: The association of vascular risk factors (VRFs) with incidence of Alzheimer's disease (AD) and vascular dementia (VaD) has been well studied. However, the association between VRFs and non-AD dementia is seldom investigated. In this study, we aim to compare the concurrence of VRFs of Lewy body dementia (LBD) to AD. Materials & Methods: We consecutively enrolled patients with dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and AD, and the prevalence of arterial hypertension, diabetes mellitus, hypercholesterolemia, hyperlipidemia, smoking, and obesity was assessed and compared...
March 2018: Brain and Behavior
https://www.readbyqxmd.com/read/29530923/endosomal-lysosomal-cholesterol-sequestration-by-u18666a-differentially-regulates-app-metabolism-in-normal-and-app-overexpressing-cells
#20
J Chung, G Phukan, D Vergote, A Mohamed, M Maulik, M Stahn, R J Andrew, G Thinakaran, E Posse de Chaves, S Kar
Amyloid β (Aβ) peptide derived from amyloid precursor protein (APP) plays a critical role in the development of Alzheimer's disease. Current evidence indicates that altered levels/subcellular distribution of cholesterol can regulate Aβ production/clearance, but it remains unclear how cholesterol sequestration within the endosomal-lysosomal (EL) system can influence APP metabolism. Thus, we evaluated the effects of U18666A, which triggers cholesterol redistribution within EL system, on mouse N2a cells expressing different levels of APP in the presence or absence of extracellular cholesterol/lipids provided by fetal bovine serum (FBS)...
March 12, 2018: Molecular and Cellular Biology
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