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Amyloid-β

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https://www.readbyqxmd.com/read/28107420/the-polyherbal-wattana-formula-displays-anti-amyloidogenic-properties-by-increasing-%C3%AE-secretase-activities
#1
Htut Htut Htoo, Suveerawan Limsuvan, Onusa Thamsermsang, Jean-François Hernandez, Frédéric Checler, Piyarat Govitrapong, Narawut Pakaprot, Pravit Akarasereenont, Bruno Vincent
Alzheimer's disease is characterized by the deposition of insoluble amyloid-β peptides produced from the β-amyloid precursor protein (βAPP). Because α-secretase cleavage by ADAM10 and ADAM17 takes place in the middle of Aβ, its activation is considered as a promising anti-AD therapeutic track. Here we establish that the polyherbal Wattana formula (WNF) stimulates sAPPα production in cells of neuronal and non-neuronal origins through an increase of both ADAM10 and ADAM17 catalytic activities with no modification of BACE1 activity and expression...
2017: PloS One
https://www.readbyqxmd.com/read/28106562/plasma-amyloid-%C3%AE-peptides-in-type-2-diabetes-a-matched-case-control-study
#2
Kirsten E Peters, Wendy A Davis, Kevin Taddei, Ralph N Martins, Colin L Masters, Timothy M E Davis, David G Bruce
BACKGROUND: Plasma amyloid-β (Aβ) levels have rarely been investigated in type 2 diabetes despite its known associations with Alzheimer's disease. OBJECTIVE: To compare blood plasma Aβ concentrations (Aβ40 and Aβ42) in cognitively normal individuals with and without type 2 diabetes. METHODS: Plasma Aβ40 and Aβ42 were measured in 194 participants with diabetes recruited from the community-based Fremantle Diabetes Study Phase II cohort (mean age 71 years, 59% males) and 194 age-, sex-, and APOEɛ4 allele-matched, control subjects without diabetes from the Australian Imaging, Biomarkers and Lifestyle Study using a multiplex microsphere-based immunoassay...
January 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106559/abca1-deficiency-affects-basal-cognitive-deficits-and-dendritic-density-in-mice
#3
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/28106556/an-improved-drugs-screening-system-reveals-that-baicalein-ameliorates-the-a%C3%AE-ampa-nmda-induced-depolarization-of-neurons
#4
Tian-Syuan Lin, Han-Jung Tsai, Chih-Han Lee, Yan-Qing Song, Rih-Sheng Huang, Hsiu-Mei Hsieh-Li, Mei-Chih Liang, Yenshou Lin
The presence of amyloid-β (Aβ) plaque and tau protein hyperphosphorylation in brain tissue is the pathological hallmark of Alzheimer's disease (AD). At least some Aβ neurotoxicity is caused by the presence of excess glutamate that has been induced by Aβ accumulation. Memantine is currently the only NMDA receptor inhibitor approved for treating moderate-to-severe AD patients. We utilized primary cortical neurons and DiBAC4(3), a slow-response voltage sensitive fluorescence dye, to create a novel system for screening herbal medicines that allows the identification of pure compounds able to ameliorate Aβ-induced abnormal depolarization...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106549/the-multimerization-state-of%C3%A2-the%C3%A2-amyloid-%C3%AE-42-amyloid-peptide-governs-its-interaction-network-with%C3%A2-the%C3%A2-extracellular-matrix
#5
Romain Salza, Claire Lethias, Sylvie Ricard-Blum
The goals of this work were i) to identify the interactions of amyloid-β (Aβ)42 under monomeric, oligomeric, and fibrillar forms with the extracellular matrix (ECM) and receptors, ii) to determine the influence of Aβ42 supramolecular organization on these interactions, and iii) to identify the molecular functions, biological processes, and pathways targeted by Aβ42 in the ECM. The ECM and cell surface partners of Aβ42 and its supramolecular forms were identified with protein and glycosaminoglycan (GAG) arrays (81 molecules in triplicate) probed by surface plasmon resonance imaging...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106548/does-the-female-advantage-in-verbal-memory-contribute-to-underestimating-alzheimer-s-disease-pathology-in-women-versus-men
#6
Erin E Sundermann, Anat Biegon, Leah H Rubin, Richard B Lipton, Susan Landau, Pauline M Maki
There is a growing recognition of sex differences in Alzheimer's disease (AD). Females show an advantage over males on tests of verbal memory, which are used to diagnose AD and its precursor, amnestic mild cognitive impairment (aMCI). Women retain this advantage in aMCI despite reduced hippocampal volume and temporal lobe glucose metabolism. Here we examined whether this female advantage endures despite evidence of AD-specific pathology, cortical amyloid-β (Aβ) deposition measured with [18F]AV45 (florbetapir) positron emission tomography...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106068/alzheimer-disease-misfolded-diabetes-mellitus-peptide-seeds-amyloid-%C3%AE-aggregation
#7
Charlotte Ridler
No abstract text is available yet for this article.
January 20, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28103595/identification-of-small-peptides-in-human-cerebrospinal-fluid-upon-amyloid-%C3%AE-degradation
#8
Naoki Mizuta, Kanta Yanagida, Takashi Kodama, Takeshi Tomonaga, Mako Takami, Hiroshi Oyama, Takashi Kudo, Manabu Ikeda, Masatoshi Takeda, Shinji Tagami, Masayasu Okochi
BACKGROUND: Amyloid-β (Aβ) degradation in brains of Alzheimer disease patients is a crucial focus for the clarification of disease pathogenesis. Nevertheless, the mechanisms underlying Aβ degradation in the human brain remain unclear. OBJECTIVE: This study aimed to quantify the levels of small C-terminal Aβ fragments generated upon Aβ degradation in human cerebrospinal fluid (CSF). METHODS: A fraction containing small peptides was isolated and purified from human CSF by high-pressure liquid chromatography...
January 20, 2017: Neuro-degenerative Diseases
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
#9
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...
January 19, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28099462/acute-and-chronic-sustained-hypoxia-do-not-substantially-regulate-amyloid-%C3%AE-peptide-generation-in-vivo
#10
Alberto Serrano-Pozo, Manuel A Sánchez-García, Antonio Heras-Garvín, Rosana March-Díaz, Victoria Navarro, Marisa Vizuete, José López-Barneo, Javier Vitorica, Alberto Pascual
BACKGROUND: Recent epidemiological evidence has linked hypoxia with the development of Alzheimer disease (AD). A number of in vitro and in vivo studies have reported that hypoxia can induce amyloid-β peptide accumulation through various molecular mechanisms including the up-regulation of the amyloid-β precursor protein, the β-secretase Bace1, or the γγ-secretase complex components, as well as the down-regulation of Aβ-degrading enzymes. OBJECTIVES: To investigate the effects of acute and chronic sustained hypoxia in Aβ generation in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28098992/mechanistic-insights-into-tunable-metal-mediated-hydrolysis-of-amyloid-%C3%AE-peptides
#11
Jeffrey S Derrick, Jiwan Lee, Shin Jung C Lee, Yujeong Kim, Eunju Nam, Hyeonwoo Tak, Juhye Kang, Misun Lee, Sun Hee Kim, Kiyoung Park, Jaeheung Cho, Mi Hee Lim
An amyloidogenic peptide, amyloid-β (Aβ), has been implicated as a contributor to the neurotoxicity of Alzheimer's disease (AD) that continues to present a major socioeconomic burden for our society. Recently, the use of metal complexes capable of cleaving peptides has arisen as an efficient tactic for amyloid management; unfortunately, little has been reported to pursue this strategy. Herein, we report a novel approach to validate the hydrolytic cleavage of divalent metal complexes toward two major isoforms of Aβ (Aβ40 and Aβ42) and tune their proteolytic activity based on the choice of metal centers (M = Co, Ni, Cu, and Zn) which could be correlated to their anti-amyloidogenic properties...
January 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28098204/strain-specific-fibril-propagation-by-an-a%C3%AE-dodecamer
#12
Dexter N Dean, Pradipta K Das, Pratip Rana, Franklin Burg, Yona Levites, Sarah E Morgan, Preetam Ghosh, Vijayaraghavan Rangachari
Low molecular weight oligomers of amyloid-β (Aβ) have emerged as the primary toxic agents in the etiology of Alzheimer disease (AD). Polymorphism observed within the aggregation end products of fibrils are known to arise due to microstructural differences among the oligomers. Diversity in aggregate morphology correlates with the differences in AD, cementing the idea that conformational strains of oligomers could be significant in phenotypic outcomes. Therefore, it is imperative to determine the ability of strains to faithfully propagate their structure...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096459/zinc-and-copper-differentially-modulate-amyloid-precursor-protein-processing-by-%C3%AE-secretase-and-amyloid-%C3%AE-peptide-production
#13
Hermeto Gerber, Fang Wu, Mitko Dimitrov, Guillermo M Garcia Osuna, Patrick C Fraering
Recent evidence suggests involvement of biometal homeostasis in the pathological mechanisms in Alzheimer's disease (AD). For example, increased intracellular copper or zinc has been linked to a reduction in secreted levels of the AD-causing amyloid-β peptide (Aβ). However, little is known about whether these biometals modulate the generation of Aβ. In the present study, we demonstrate in both cell-free and cell-based assays that zinc and copper regulate Aβ production by distinct molecular mechanisms affecting the processing by γ-secretase of its Aβ precursor protein substrate APP-C99...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096372/helical-structure-stability-and-dynamics-in-human-apolipoprotein-e3-and-e4-by-hydrogen-exchange-and-mass-spectrometry
#14
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 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28094952/effect-of-an-enhanced-nose-to-brain-delivery-of-insulin-on-mild-and-progressive-memory-loss-in-the-senescence-accelerated-mouse
#15
Noriyasu Kamei, Misa Tanaka, Hayoung Choi, Nobuyuki Okada, Takamasa Ikeda, Rei Itokazu, Mariko Takeda-Morishita
Insulin is now considered to be a new drug candidate for treating dementias, such as Alzheimer's disease, whose pathologies are linked to insulin resistance in the brain. Our recent work has clarified that a noncovalent strategy involving cell-penetrating peptides (CPPs) can increase the direct transport of insulin from the nasal cavity into the brain parenchyma. The present study aimed to determine whether the brain insulin level increased by intranasal coadministration of insulin with the CPP penetratin has potential for treating dementia...
January 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28093855/typical-and-atypical-appearance-of-early-onset-alzheimer-s-disease-a-clinical-neuroimaging-and-neuropathological-study-symposium-fundamentals-learned-from-diversity-among-typical-and-atypical-appearances
#16
Shinobu Kawakatsu 川勝 忍, Ryota Kobayashi, Hiroshi Hayashi
The International Working Group (IWG) has classified Alzheimer's disease (AD) as two different types, the typical form and the atypical form, but clinicopathological studies of atypical AD are limited. Because atypical AD cases usually present with early-onset dementia, we investigated 12 patients with early-onset AD, including two patients with typical AD and 10 patients with atypical AD. Of these patients, six had the posterior variant, three had the frontal variant and one had the logopenic variant mixed with semantic dementia...
January 17, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28087694/iso-%C3%AE-acids-bitter-components-of-beer-prevent-inflammation-and-cognitive-decline-induced-in-a-mouse-model-of-alzheimer-s-disease
#17
Yasuhisa Ano, Atsushi Dhata, Yoshimasa Taniguchi, Ayaka Hoshi, Kazuyuki Uchida, Akihiko Takashima, Hiroyuki Nakayama
Alongside the rapid growth in aging populations worldwide, prevention and therapy for age-related memory decline and dementia are in great demand to maintain a long healthy life. Here we found that iso-α-acids, hop-derived bitter compounds in beer, enhance microglial phagocytosis and suppress inflammation via activation of the peroxisome proliferator-activated receptor (PPAR-γ). In normal mice, oral administration of iso-α-acids led to a significant increase both in CD11b and CD206 double-positive anti-inflammatory type microglia (P<0...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28077397/relationships-between-flortaucipir-pet-tau-binding-and-amyloid-burden-clinical-diagnosis-age-and-cognition
#18
Michael J Pontecorvo, Michael D Devous, Michael Navitsky, Ming Lu, Stephen Salloway, Frederick W Schaerf, Danna Jennings, Anupa K Arora, Anne McGeehan, Nathaniel C Lim, Hui Xiong, Abhinay D Joshi, Andrew Siderowf, Mark A Mintun
The advent of tau-targeted positron emission tomography tracers such as flortaucipir ((18)F-AV-1451, also known as (18)F-T807) have made it possible to investigate the sequence of development of tau and amyloid-β in relationship to age, and to the development of cognitive impairment due to Alzheimer's disease. In this study, flortaucipir tau and florbetapir amyloid positron emission tomography were obtained for 217 subjects including 16 young and 58 older cognitively normal subjects, 95 subjects with mild cognitive impairment (Mini-Mental State Examination 24-30) and 48 subjects with clinically-defined possible or probable Alzheimer's disease (Mini-Mental State Examination >10)...
January 11, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28077289/vitamin-d3-protects-against-a%C3%AE-peptide-cytotoxicity-in-differentiated-human-neuroblastoma-sh-sy5y-cells-a-role-for-s1p1-p38mapk-atf4-axis
#19
Federica Pierucci, Mercedes Garcia-Gil, Alessia Frati, Francesca Bini, Maria Martinesi, Eleonora Vannini, Marco Mainardi, Federico Luzzati, Paolo Peretto, Matteo Caleo, Elisabetta Meacci
Besides its classical function of bone metabolism regulation, 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3), acts on a variety of tissues including the nervous system, where the hormone plays an important role as neuroprotective, antiproliferating and differentiating agent. Sphingolipids are bioactive lipids that play critical and complex roles in regulating cell fate. In the present paper we have investigated whether sphingolipids are involved in the protective action of 1,25(OH)2D3. We have found that 1,25(OH)2D3 prevents amyloid-β peptide (Aβ(1-42)) cytotoxicity both in differentiated SH-SY5Y human neuroblastoma cells and in vivo...
January 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28073379/tau-passive-immunization-inhibits-not-only-tau-but-also-a%C3%AE-pathology
#20
Chun-Ling Dai, Yunn Chyn Tung, Fei Liu, Cheng-Xin Gong, Khalid Iqbal
BACKGROUND: Accumulation of hyperphosphorylated tau protein is a histopathological hallmark of Alzheimer's disease (AD) and related tauopathies. Currently, there is no effective treatment available for these progressive neurodegenerative diseases. In recent years, tau immunotherapy has shown great potential in animal models. We report the effect of immunization with tau antibodies 43D against tau 6-18 and 77E9 against tau 184-195 on tau and amyloid-β (Aβ) pathologies and cognition in triple-transgenic (3×Tg)-AD mice at mild to moderate stages of the disease...
January 10, 2017: Alzheimer's Research & Therapy
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