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https://www.readbyqxmd.com/read/27921029/nanoscale-structure-and-spectroscopic-probing-of-a%C3%AE-1-40-fibril-bundle-formation
#1
Katarzyna M Psonka-Antonczyk, Per Hammarström, Leif B G Johansson, Mikael Lindgren, Bjørn T Stokke, K Peter R Nilsson, Sofie Nyström
Amyloid plaques composed of fibrillar Amyloid-β (Aβ) are hallmarks of Alzheimer's disease. However, Aβ fibrils are morphologically heterogeneous. Conformation sensitive luminescent conjugated oligothiophenes (LCOs) are versatile tools for monitoring such fibril polymorphism in vivo and in vitro. Biophysical methods applied on in vitro generated Aβ fibrils, stained with LCOs with different binding and fluorescence properties, can be used to characterize the Aβ fibrillation in depth, far beyond that possible for in vivo generated amyloid plaques...
2016: Frontiers in Chemistry
https://www.readbyqxmd.com/read/27919712/extracts-from-two-ubiquitous-mediterranean-plants-ameliorate-cellular-and-animal-models-of-neurodegenerative-proteinopathies
#2
Michelle Briffa, Stephanie Ghio, Johanna Neuner, Alison J Gauci, Rebecca Cacciottolo, Christelle Marchal, Mario Caruana, Christophe Cullin, Neville Vassallo, Ruben J Cauchi
A signature feature of age-related neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-β (Aβ) in Alzheimer's disease (AD) and α-synuclein (α-syn) in Parkinson's disease (PD), into soluble oligomeric structures that are highly neurotoxic. Cellular and animal models that faithfully replicate the hallmark features of these disorders are being increasing exploited to identify disease-modifying compounds. Natural compounds have been identified as a useful source of bioactive molecules with promising neuroprotective capabilities...
December 2, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27917876/soluble-amyloid-beta-aggregates-from-human-alzheimer-s-disease-brains
#3
Thomas J Esparza, Norelle C Wildburger, Hao Jiang, Mihika Gangolli, Nigel J Cairns, Randall J Bateman, David L Brody
Soluble amyloid-beta (Aβ) aggregates likely contribute substantially to the dementia that characterizes Alzheimer's disease. However, despite intensive study of in vitro preparations and animal models, little is known about the characteristics of soluble Aβ aggregates in the human Alzheimer's disease brain. Here we present a new method for extracting soluble Aβ aggregates from human brains, separating them from insoluble aggregates and Aβ monomers using differential ultracentrifugation, and purifying them >6000 fold by dual antibody immunoprecipitation...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917428/ftir-imaging-of-the-molecular-burden-around-a%C3%AE-deposits-in-an-early-stage-3-tg-app-psp1-tau-mouse-model-of-alzheimer-s-disease
#4
Artur Dawid Surowka, Michael Pilling, Alex Henderson, Herve Boutin, Lidan Christie, Magdalena Szczerbowska-Boruchowska, Peter Gardner
Alzheimer's disease is one of the major causes of dementia in the elderly. The disease is caused by the misfolding of water soluble alpha-helical proteins, which leads to the accumulation of β-sheets in the form of amyloid plaques, which can subsequently affect surrounding tissue areas by oxidative stress neurotoxicity. The aim of the present study was to design a novel methodology to analyze the extent to the neuronal burden around protein-rich Aβ plaques suspected to affect molecular components by oxidative stress induced by inflammatory states...
December 5, 2016: Analyst
https://www.readbyqxmd.com/read/27917270/effect-of-creatine-supplementation-on-cognitive-performance-and-apoptosis-in-a-rat-model-of-amyloid-beta-induced-alzheimer-s-disease
#5
Malek Alimohammadi-Kamalabadi, Mohammadreza Eshraghian, Mohammad-Reza Zarindast, Abbas Aliaghaei, Hamideh Pishva
OBJECTIVES: Neuroprotective effect of creatine (Cr) against β-amyloid (Aβ) is reported in an in vitro study. This study investigated the effect of Cr supplementation on β-amyloid toxicity in vivo. MATERIALS AND METHODS: Thirty two, male Wistar rats were divided into 4 groups. During ten weeks of study, control group went through no surgical or dietary intervention. At the 4th week of study Sham group had a hippocampal normal saline injection, while Aβ and AβCr groups had an β-amyloid injection in the hippocampus...
November 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27917152/amyloid-dysmetabolism-relates-to-reduced-glucose-uptake-in-white-matter-hyperintensities
#6
Lisa Flem Kalheim, Per Selnes, Atle Bjørnerud, Christopher Coello, Kjetil Vegge, Tormod Fladby
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and cause of dementia and is characterized by amyloid plaques and neurofibrillary tangles. AD has traditionally been considered to primarily affect gray matter, but multiple lines of evidence also indicate white matter (WM) pathology and associated small-vessel cerebrovascular disease. WM glucose delivery and metabolism may have implications for local tissue integrity, and [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) may be helpful to assess neuroglial and axonal function in WM...
2016: Frontiers in Neurology
https://www.readbyqxmd.com/read/27915995/lack-of-p-glycoprotein-results-in-impairment-of-removal-of-beta-amyloid-and-increased-intraparenchymal-cerebral-amyloid-angiopathy-after-active-immunization-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#7
Sascha Brückmann, Anja Brenn, Markus Grube, Katharina Niedrig, Silva Holtfreter, Oliver von Bohlen Und Halbach, Martin Groschup, Markus Keller, Silke Vogelgesang
Immunization against beta-amyloid (Aβ) reduces cerebral Aβ deposits and improves cognitive capacities in transgenic mouse models, and thus has been considered a promising disease-modifying therapeutic approach for Alzheimer's disease (AD). Although clinical trials in AD patients have yielded evidence for clearance of parenchymal Aβ plaques, Aβ increases in blood vessels of treated patients. We hypothesize that an age-related decline in the mechanisms that clear Aβ from the brain might be at least in part responsible for the failure to purge and re-distribute Aβ...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27914799/computational-approach-for-the-assessment-of-inhibitory-potency-against-beta-amyloid-aggregation
#8
Marek Bajda, Sławomir Filipek
Beta-amyloid (Aβ) plaques are one of the hallmarks of Alzheimer's disease. Their presence in the brain leads to neurodegeneration and memory decline. Therefore, search for new drugs able to decrease formation of such deposits is of great interest. Our previously developed multifunctional compounds inhibited transformation of monomers into fibrils. Herein, we describe the computational approach for the assessment of inhibitory activity against Aβ aggregation. The influence of novel inhibitors on amyloid Aβ17-42 was studied by employing of molecular docking and all-atom molecular dynamics simulations...
November 24, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27913965/plasma-amyloid-beta-levels-in-patients-with-different-types-of-cancer
#9
Wang-Sheng Jin, Xian-Le Bu, Yu-Hui Liu, Lin-Lin Shen, Zhen-Qian Zhuang, Shu-Sheng Jiao, Chi Zhu, Qing-Hua Wang, Hua-Dong Zhou, Tao Zhang, Yan-Jiang Wang
Several epidemiological investigations indicate that cancer survivors have a lower risk for Alzheimer's disease (AD) and vice versa. However, the associations between plasma amyloid-beta (Aβ) levels with cancer remain largely unknown. In this case-control study, 110 cancer patients, 70 AD patients, and 70 age- and gender-matched normal controls were recruited. The cancer types include esophagus cancer, colorectal cancer, hepatic cancer, and lung cancer, all of which were reported to be associated with a lower risk for AD...
December 3, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27913964/intracerebroventricular-streptozotocin-as-a-model-of-alzheimer-s-disease-neurochemical-and-behavioral-characterization-in-mice
#10
Katherine Garcia Ravelli, Barbara Dos Anjos Rosário, Rosana Camarini, Marina Sorrentino Hernandes, Luiz Roberto Britto
Streptozotocin has been widely used to mimic some aspects of Alzheimer's disease (AD). However, especially in mice, several characteristics involved in the streptozotocin (STZ)-induced AD pathology are not well known. The main purpose of this study was to evaluate temporally the expression of AD-related proteins, such as amyloid-β (Aβ), choline acetyltransferase (ChAT), synapsin, axonal neurofilaments, and phosphorylated Tau in the hippocampus following intracerebroventricular (icv) administration of STZ in adult mice...
December 2, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27911757/local-and-use-dependent-effects-of-%C3%AE-amyloid-oligomers-on-nmda-receptor-function-revealed-by-optical-quantal-analysis
#11
Brooke L Sinnen, Aaron B Bowen, Emily S Gibson, Matthew J Kennedy
: Beta amyloid (Aβ) triggers the elimination of excitatory synaptic connections in the CNS, an early manifestation of Alzheimer's disease. Oligomeric assemblies of Aβ peptide associate with excitatory synapses resulting in synapse elimination through a process that requires NMDA-type glutamate receptor activation. Whether Aβ affects synaptic NMDA receptor (NMDAR) function directly and acts locally at synapses to which it has bound and whether synaptic activity influences Aβ synaptic binding and synaptotoxicity have remained fundamental questions...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27911326/localization-and-processing-of%C3%A2-the%C3%A2-amyloid-%C3%AE-protein-precursor-in%C3%A2-mitochondria-associated-membranes
#12
Dolores Del Prete, Jan M Suski, Bénédicte Oulès, Delphine Debayle, Anne Sophie Gay, Sandra Lacas-Gervais, Renaud Bussiere, Charlotte Bauer, Paolo Pinton, Patrizia Paterlini-Bréchot, Mariusz R Wieckowski, Frédéric Checler, Mounia Chami
Alteration of mitochondria-associated membranes (MAMs) has been proposed to contribute to the pathogenesis of Alzheimer's disease (AD). We studied herein the subcellular distribution, the processing, and the protein interactome of the amyloid-β protein precursor (AβPP) and its proteolytic products in MAMs. We reveal that AβPP and its catabolites are present in MAMs in cellular models overexpressing wild type AβPP or AβPP harboring the double Swedish or London familial AD mutations, and in brains of transgenic mice model of AD...
November 26, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911324/proteomics-analysis-of-blood-serums-from-alzheimer-s-disease-patients-using-itraq-labeling-technology
#13
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/27911312/increased-transforming-growth-factor-%C3%AE-2-in-the-neocortex-of-alzheimer-s-disease-and-dementia-with-lewy-bodies-is%C3%A2-correlated-with-disease-severity-and%C3%A2-soluble-a%C3%AE-42-load
#14
Joyce R Chong, Yuek Ling Chai, Jasinda H Lee, David Howlett, Johannes Attems, Clive G Ballard, Dag Aarsland, Paul T Francis, Christopher P Chen, Mitchell K P Lai
BACKGROUND: Of the three transforming growth factor (TGF)-β isoforms known, TGFβ1 deficits have been widely reported in Alzheimer's disease (AD) and studied as a potential therapeutic target. In contrast, the status of TGFβ2, which has been shown to mediate amyloid-β (Aβ)-mediated neuronal death, are unclear both in AD and in Lewy body dementias (LBD) with differential neuritic plaque and neurofibrillary tangle burden. OBJECTIVE: To measure neocortical TGFβ2 levels and their correlations with neuropathological and clinical markers of disease severity in a well-characterized cohort of AD as well as two clinical subtypes of LBD, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), known to manifest relatively high and low Aβ plaque burden, respectively...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911295/efficacy-and-safety-of-plasma-exchange-with-5-albumin-to-modify-cerebrospinal-fluid-and-plasma-amyloid-%C3%AE-concentrations-and-cognition-outcomes-in%C3%A2-alzheimer-s-disease-patients-a%C3%A2-multicenter-randomized-controlled-clinical-trial
#15
Mercè Boada, Fernando Anaya, Pilar Ortiz, Javier Olazarán, Joshua R Shua-Haim, Thomas O Obisesan, Isabel Hernández, Joan Muñoz, Mar Buendia, Montserrat Alegret, Asunción Lafuente, Lluís Tárraga, Laura Núñez, Mireia Torres, Joan Ramon Grifols, Isidre Ferrer, Oscar L Lopez, Antonio Páez
BACKGROUND: Studies conducted in animal models and humans suggest the presence of a dynamic equilibrium of amyloid-β (Aβ) peptide between cerebrospinal fluid (CSF) and plasma compartments. OBJECTIVE: To determine whether plasma exchange (PE) with albumin replacement was able to modify Aβ concentrations in CSF and plasma as well as to improve cognition in patients with mild-moderate Alzheimer's disease (AD). METHODS: In a multicenter, randomized, patient- and rater-blind, controlled, parallel-group, phase II study, 42 AD patients were assigned (1 : 1) to PE treatment or control (sham) groups...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911291/a-metal-free-method-for-producing-mri-contrast-at-amyloid-%C3%AE
#16
Silvia Hilt, Tang Tang, Jeffrey H Walton, Madhu Budamagunta, Izumi Maezawa, Tamás Kálai, Kálmán Hideg, Vikrant Singh, Heike Wulff, Qizhi Gong, Lee-Way Jin, Angelique Louie, John C Voss
Alzheimer's disease (AD) is characterized by depositions of the amyloid-β (Aβ) peptide in the brain. The disease process develops over decades, with substantial neurological loss occurring before a clinical diagnosis of dementia can be rendered. It is therefore imperative to develop methods that permit early detection and monitoring of disease progression. In addition, the multifactorial pathogenesis of AD has identified several potential avenues for AD intervention. Thus, evaluation of therapeutic candidates over lengthy trial periods also demands a practical, noninvasive method for measuring Aβ in the brain...
November 26, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911290/rare-genetic-variant-in-sorl1-may-increase-penetrance-of-alzheimer-s-disease-in-a-family-with-several-generations-of-apoe-%C3%A9-4-homozygosity
#17
Eva Louwersheimer, Petra E Cohn-Hokke, Yolande A L Pijnenburg, Marjan M Weiss, Erik A Sistermans, Annemieke J Rozemuller, Marc Hulsman, John C van Swieten, Cock M van Duijn, Frederik Barkhof, Teddy Koene, Philip Scheltens, Wiesje M Van der Flier, Henne Holstege
BACKGROUND: The major genetic risk factor for late onset Alzheimer's disease (AD) is the APOE-ɛ4 allele. However, APOE-ɛ4 homozygosity is not fully penetrant, suggesting co-occurrence of additional genetic variants. OBJECTIVE: To identify genetic factors that, next to APOE-ɛ4 homozygosity, contribute to the development of AD. METHODS: We identified a family with nine AD patients spanning four generations, with an inheritance pattern suggestive of autosomal dominant AD, with no variants in PSEN1, PSEN2, or APP...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911289/the-brain-s-structural-connectome-mediates-the-relationship-between-regional-neuroimaging-biomarkers-in%C3%A2-alzheimer-s-disease
#18
Sneha Pandya, Amy Kuceyeski, Ashish Raj
Alzheimer's disease (AD), one of the most common causes of dementia in adults, is a progressive neurodegenerative disorder exhibiting well-defined neuropathological hallmarks. It is known that disease pathology involves misfolded amyloid-β (Aβ) and tau proteins, and exhibits a relatively stereotyped progression over decades. The relationship between AD neuropathological hallmarks (Aβ, hypometabolism, and tau proteins) and imaging biomarkers (MRI, AV-45/FDG-PET) is not fully understood. In addition, biomarker pathologies are oftentimes discordant, wherein it may show varying levels of abnormality across brain regions...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911039/para-sulfonato-calix-n-arenes-inhibit-amyloid-beta-peptide-fibrillation-and-reduce-amyloid-cytotoxicity
#19
Ziyuan Wang, Shipeng Tao, Xiaoyan Dong, Yan Sun
Amyloid β-peptides (Aβ) fibrillation is a major hallmark of Alzheimer's disease (AD). Inhibition of Aβ fibrillation is thus considered as an effective strategy for AD prevention and treatment. Here we show that para-sulfonato-calix[n]arenes (SC[n]A, n=4, 6, 8), a class of amphiphilic calixarene derivatives, can bind to Aβ42 through nonspecific and multipoint hydrophobic interactions. Their binding leads to a pronounced delay in β-sheet adoption and formation of multiple secondary structures of the peptide, accompanied by changes at the level of the fibrillary architecture...
December 2, 2016: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/27909447/stem-cell-therapy-a-prospective-treatment-for-alzheimer-s-disease
#20
REVIEW
Ji Han Lee, Il-Hoan Oh, Hyun Kook Lim
Alzheimer's disease (AD) without cure remains as a serious health issue in the modern society. The major neuropathological alterations in AD are characterized by chronic neuroinflammation and neuronal loss due to neurofibrillary tangles (NFTs) of abnormally hyperphosphorylated tau, plaques of β-amyloid (Aβ) and various metabolic dysfunctions. Due to the multifaceted nature of AD pathology and our limited understanding on its etiology, AD is difficult to be treated with currently available pharmaceuticals...
November 2016: Psychiatry Investigation
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