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https://www.readbyqxmd.com/read/28346578/association-of-plasma-neurofilament-light-with-neurodegeneration-in-patients-with-alzheimer-disease
#1
Niklas Mattsson, Ulf Andreasson, Henrik Zetterberg, Kaj Blennow
Importance: Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive or expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker for neurodegeneration in dementias. Objective: To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration...
March 27, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28346227/reducing-expression-of-synapse-restricting-protein-ephexin5-ameliorates-alzheimer-s-like-impairment-in-mice
#2
Gabrielle L Sell, Thomas B Schaffer, Seth S Margolis
Accumulation of amyloid-β (Aβ) protein may cause synapse degeneration and cognitive impairment in Alzheimer's disease (AD) by reactivating expression of the developmental synapse repressor protein Ephexin5 (also known as ARHGEF15). Here, we have reported that Aβ is sufficient to acutely promote the production of Ephexin5 in mature hippocampal neurons and in mice expressing human amyloid precursor protein (hAPP mice), a model for familial AD that produces high brain levels of Aβ. Ephexin5 expression was highly elevated in the hippocampi of human AD patients, indicating its potential relevance to AD...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28345062/secondary-structure-propensity-and-chirality-of-the-amyloidophilic-peptide-p5-and-its-analogues-impacts-ligand-binding-in-vitro-characterization
#3
Jonathan S Wall, Angela Williams, Craig Wooliver, Emily B Martin, Xiaolin Cheng, R Eric Heidel, Stephen J Kennel
BACKGROUND: Polybasic helical peptides, such as peptide p5, bind human amyloid extracts and synthetic amyloid fibrils. When radiolabeled, peptide p5 has been shown to specifically bind amyloid in vivo thereby allowing imaging of the disease. Structural requirements for heparin and amyloid binding have been studied using analogs of p5 that modify helicity and chirality. METHODS: Peptide-ligand interactions were studied using CD spectroscopy and solution-phase binding assays with radiolabeled p5 analogs...
December 2016: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28344547/app-function-and-lipids-a-bidirectional-link
#4
REVIEW
Marcus O W Grimm, Janine Mett, Heike S Grimm, Tobias Hartmann
Extracellular neuritic plaques, composed of aggregated amyloid-β (Aβ) peptides, are one of the major histopathological hallmarks of Alzheimer's disease (AD), a progressive, irreversible neurodegenerative disorder and the most common cause of dementia in the elderly. One of the most prominent risk factor for sporadic AD, carrying one or two aberrant copies of the apolipoprotein E (ApoE) ε4 alleles, closely links AD to lipids. Further, several lipid classes and fatty acids have been reported to be changed in the brain of AD-affected individuals...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28342849/comparative-effects-of-etoh-consumption-and-thiamine-deficiency-on-cognitive-impairment-oxidative-damage-and-%C3%AE-amyloid-peptide-overproduction-in-the-brain
#5
Yu-Shi Gong, Kun Hu, Lu-Qi Yang, Juan Guo, Yong-Qing Gao, Feng-Lin Song, Fang-Li Hou, Cui-Yi Liang
The effects of chronic EtOH consumption, associated or not with thiamine deficiency (TD), on cognitive impairment, oxidative damage, and β-amyloid (Aβ) peptide accumulation in the brain were investigated in male C57BL/6 mice. We established an alcoholic mouse model by feeding an EtOH liquid diet, a TD mouse model by feeding a thiamine-depleted liquid diet, and an EtOH treatment associated with TD mouse model by feeding a thiamine-depleted EtOH liquid diet for 7 weeks. The learning and memory functions of the mice were detected through the Y-maze test...
March 22, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28342697/recent-publications-from-the-alzheimer-s-disease-neuroimaging-initiative-reviewing-progress-toward-improved-ad-clinical-trials
#6
REVIEW
Michael W Weiner, Dallas P Veitch, Paul S Aisen, Laurel A Beckett, Nigel J Cairns, Robert C Green, Danielle Harvey, Clifford R Jack, William Jagust, John C Morris, Ronald C Petersen, Andrew J Saykin, Leslie M Shaw, Arthur W Toga, John Q Trojanowski
INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the 450+ publications using ADNI data during 2014 and 2015. METHODS: We used standard searches to find publications using ADNI data. RESULTS: (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses...
March 22, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28342294/benzylphenylpyrrolizinones-with-anti-amyloid-and-scavenging-effects-potentially-useful-in-alzheimer-s-disease-treatment
#7
Jean-Pierre Gabriel Jourdan, Marc Since, Laîla El Kihel, Cédric Lecoutey, Sophie Corvaisier, Rémi Legay, Jana Sopkova-de Oliveira Santos, Thierry Cresteil, Aurélie Malzert-Fréon, Christophe Rochais, Patrick Dallemagne
This article describes the drug design steps developed to try to increase the scavenging and Aβ aggregation inhibition activities of a previously described series of benzylidenephenyl-pyrrolizinones. Among the novel synthesized derivatives, some benzylphenylpyrrolizinones exhibited interesting results in regard to those activities and first druggability parameters which confer to these compounds a potential therapeutic interest in Alzheimer's disease.
March 25, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28342211/the-molecular-behavior-of-a-single-%C3%AE-amyloid-inside-a-dipalmitoylphosphatidylcholine-bilayer-at-three-different-temperatures-an-atomistic-simulation-study
#8
Faezeh Kargar, Saeed Emadi, Hossein Fazli
The behavior of a single Aβ40 molecule within a dipalmitoylphosphatidylcholine (DPPC) bilayer was studied by all-atom molecular dynamics simulations. The effect of membrane structure was investigated on Aβ40 behavior, secondary structure and insertion depth. Simulations were performed at three temperatures (323, 310 and 300 K) to probe three different bilayer fluidities. Results show that at all above temperatures the peptide contains two short helices, coil, bend and turn structures. At 300 K, the peptide contains a region with β structure in C-terminal region...
March 25, 2017: Proteins
https://www.readbyqxmd.com/read/28340576/polysaccharides-from-ganoderma-lucidum-attenuate-microglia-mediated-neuroinflammation-and-modulate-microglial-phagocytosis-and-behavioural-response
#9
Qing Cai, Yuanyuan Li, Gang Pei
BACKGROUND: Ganoderma lucidum (GL) has been widely used in Asian countries for hundreds of years to promote health and longevity. The pharmacological functions of which had been classified, including the activation of innate immune responses, suppression of tumour and modulation of cell proliferations. Effective fractions of Ganoderma lucidum polysaccharides (GLP) had already been reported to regulate the immune system. Nevertheless, the role of GLP in the microglia-mediated neuroinflammation has not been sufficiently elucidated...
March 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28340507/understanding-the-contribution-of-disulphide-bridges-to-the-folding-and-misfolding-of-an-anti-a%C3%AE-scfv
#10
Laia Montoliu-Gaya, Jose C Martínez, Sandra Villegas
ScFv-h3D6 is a single chain variable fragment that precludes Aβ peptide-induced cytotoxicity by withdrawing Aβ oligomers from the amyloid pathway to the worm-like pathway. Production of scFv molecules is not a straightforward procedure because of the occurrence of disulphide scrambled conformations generated in the refolding process. Here, we separately removed the disulphide bond of each domain and solved the scrambling problem; and then, we intended to compensate the loss of thermodynamic stability by adding three C-terminal elongation mutations previously described to stabilize the native fold of scFv-h3D6...
March 24, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28339396/modulation-of-a%C3%AE-pp-and-gsk3%C3%AE-by-endoplasmic-reticulum-stress-and-involvement-in-alzheimer-s-disease
#11
Xin-Jun Liu, Jun Wei, Ying-Hui Shang, Han-Chang Huang, Feng-Xue Lao
Alzheimer's disease (AD) is a dementia disease with neuronal loss and synaptic impairment. This impairment is caused, at least partly, by the generation of two main AD hallmarks, namely the hyperphosphorylated tau protein comprising neurofibrillary tangles and senile plaques containing amyloid-β (Aβ) peptides. The amyloid-β protein precursor (AβPP) and glycogen synthase kinase-3β (GSK3β) are two main proteins associated with AD and are closely correlated with these hallmarks. Recently, both of the proteins were reported to be modulated by endoplasmic reticulum stress (ERS) and are involved in the pathogenesis of AD...
March 20, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28337747/structure-dependent-effects-of-amyloid-%C3%AE-on-long-term-memory-in-lymnaea-stagnalis
#12
Lenzie Ford, Michael Crossley, Devkee M Vadukul, György Kemenes, Louise C Serpell
Amyloid-β (Aβ) peptides are implicated in the causation of memory loss, neuronal impairment, and neurodegeneration in Alzheimer's disease. Our recent work revealed that Aβ 1-42 and Aβ 25-35 inhibit long-term memory (LTM) recall in Lymnaea stagnalis (pond snail) in the absence of cell death. Here, we report the characterization of the active species prepared under different conditions, describe which Aβ species is present in brain tissue during the behavioral recall time point and relate the sequence and structure of the oligomeric species to the resulting neuronal properties and effect on LTM...
March 24, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28337497/dimerization-and-conformation-related-free-energy-landscapes-of-dye-tagged-amyloid-%C3%AE-12-28-linked-to-fret-experiments
#13
Alexander Kulesza, Steven Daly, Philippe Dugourd
We have investigated the free energy landscape of Aβ-peptide dimer models in connection to gas-phase FRET experiments. We use a FRET-related distance coordinate and one conformation-related coordinate per monomer for accelerated structural exploration with well-tempered metadynamics in solvent and in vacuo. The free energy profiles indicate that FRET under equilibrium conditions should be significantly affected by the de-solvation upon the transfer of ions to the gas-phase. In contrast, a change in the protonation state is found to be less impacting once de-solvated...
March 24, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28337142/icariside-ii-effectively-reduces-spatial-learning-and-memory-impairments-in-alzheimer-s-disease-model-mice-targeting-beta-amyloid-production
#14
Lingli Yan, Yuanyuan Deng, Jianmei Gao, Yuangui Liu, Fei Li, Jingshan Shi, Qihai Gong
Icariside II (ICS II) is a broad-spectrum anti-cancer natural compound extracted from Herba Epimedii Maxim. Recently, the role of ICS II has been investigated in central nervous system, especially have a neuroprotective effect in Alzheimer's disease (AD). In this study, we attempted to investigate the effects of ICS II, on cognitive deficits and beta-amyloid (Aβ) production in APPswe/PS1dE9 (APP/PS1) double transgenic mice. It was found that chronic ICS II administrated not only effectively ameliorated cognitive function deficits, but also inhibited neuronal degeneration and reduced the formation of plaque burden...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28336779/validation-of-the-semi-quantitative-static-suvr-method-for-18-f-av45-pet-by-pharmacokinetic-modeling-with-an-arterial-input-function
#15
Julie Ottoy, Jeroen Verhaeghe, Ellis Niemantsverdriet, Leonie Wyffels, Charisse Somers, Ellen De Roeck, Hanne Struyfs, Femke Soetewey, Steven Deleye, Tobi Van den Bossche, Sara Van Mossevelde, Sarah Ceyssens, Jan Versijpt, Sigrid Stroobants, Sebastiaan Engelborghs, Steven Staelens
Increased brain uptake of [(18)F]-AV45 visualized by PET is a key biomarker for Alzheimer's disease (AD). The standardized uptake value ratio (SUVR) is widely used for quantification, but is subject to variability based on choice of reference region and changes in cerebral blood flow. Here we validate the SUVR method against the gold standard volume of distribution (VT) to assess cross-sectional differences in plaque load. Methods: Dynamic 60-min [(18)F]-AV45 (291 ± 67 MBq) and 1-min [(15)O]-H2O (370 MBq) scans were obtained in 35 age-matched elderly subjects, including 10 probable AD dementia, 15 amnestic mild cognitive impairment (aMCI) and 10 cognitively healthy controls (HC)...
March 23, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28336494/minocycline-reduces-inflammatory-parameters-in-the-brain-structures-and-serum-and-reverses-memory-impairment-caused-by-the-administration-of-amyloid-%C3%AE-1-42-in-mice
#16
Michelle Lima Garcez, Francielle Mina, Tatiani Bellettini-Santos, Franciellen Gonçalves Carneiro, Aline Pereira da Luz, Gustavo Luis Schiavo, Matheus Scopel Andrighetti, Maylton Grégori Scheid, Renan Pereira Bolfe, Josiane Budni
Alzheimer's disease (AD) is a neurodegenerative disorder and the most common type of age-related dementia. Cognitive decline, beta-amyloid (Aβ) accumulation, neurofibrillary tangles, and neuroinflammation are the main pathophysiological characteristics of AD. Minocycline is a tetracycline derivative with anti-inflammatory properties that has a neuroprotective effect. The aim of this study was to evaluate the effect of minocycline on memory, neurotrophins and neuroinflammation in an animal model of AD induced by the administration of Aβ (1-42) oligomer...
March 20, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28336338/knockdown-of-appl-mimics-transgenic-a%C3%AE-induced-neurodegenerative-phenotypes-in-drosophila
#17
Sandeep Kumar Singh, Saurabh Srivastav, Amarish Kumar Yadav, Saripella Srikrishna
A variety of Drosophila mutant lines have been established as potential disease-models to study various disease mechanisms including human neurodegenerative diseases like Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD). The evolutionary conservation of APP (Amyloid Precursor Protein) and APPL (Amyloid Precursor Protein-Like) and the comparable detrimental effects caused by their metabolic products strongly implies the conservation of their normal physiological functions. In view of this milieu, a comparative analysis on the pattern of neurodegenerative phenotypes between Drosophila APPL-RNAi line and transgenic Drosophila line expressing eye tissue specific human Aβ (Amyloid beta) was undertaken...
March 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28334897/genetic-absence-of-alox5-protects-from-homocysteine-induced-memory-impairment-tau-phosphorylation-and-synaptic-pathology
#18
Jian-Guo Li, Carlos Barrero, Salim Merali, Domenico Praticò
Elevated level of homocysteine (Hcy) is considered a risk factor for neurodegenerative diseases, but the mechanisms remain to be established. Since high Hcy is associated with an up-regulation of the ALOX5 gene product, the 5Lipoxygenase (5LO), herein we investigated whether this activation is responsible for the Hcy effect on neurodegeneration or is a secondary event.To reach this goal, wild type mice and mice genetically deficient for 5LO were assessed after being exposed to a diet known to significantly increase brain levels of Hcy...
March 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28332604/phenotype-of-postural-instability-gait-difficulty-in-parkinson-disease-relevance-to-cognitive-impairment-and-mechanism-relating-pathological-proteins-and-neurotransmitters
#19
Li-Jun Zuo, Ying-Shan Piao, Li-Xia Li, Shu-Yang Yu, Peng Guo, Yang Hu, Teng-Hong Lian, Rui-Dan Wang, Qiu-Jin Yu, Zhao Jin, Ya-Jie Wang, Xiao-Min Wang, Piu Chan, Sheng-Di Chen, Yong-Jun Wang, Wei Zhang
Parkinson disease (PD) is identified as tremor-dominant (TD) and postural instability and gait difficulty (PIGD) phenotypes. The relationships between motor phenotypes and cognitive impairment and the underlying mechanisms relating pathological proteins and neurotransmitters in cerebrospinal fluid (CSF) are unknown. We evaluated the motor symptoms and cognitive function by scales, and detected the levels of pathological proteins and neurotransmitters in CSF. TD group and PIGD group had significantly higher levels of total tau, tau phosphorylated at the position of threonine 181(P-tau181t), threonine 231, serine 396, serine 199 and lower β amyloid (Aβ)1-42 level in CSF than those in control group; PIGD group had significantly higher P-tau181t level and lower Aβ1-42 level than those in TD group...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332351/metabolism-centric-overview-of-the-pathogenesis-of-alzheimer-s-disease
#20
REVIEW
Somang Kang, Yong Ho Lee, Jong Eun Lee
Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia. AD is characterized by the extracellular amyloid beta (Aβ) plaques and intraneuronal deposits of neurofibrillary tangles (NFTs). Recently, as aging has become a familiar phenomenon around the world, patients with AD are increasing in number. Thus, many researchers are working toward finding effective therapeutics for AD focused on Aβ hypothesis, although there has been no success yet. In this review paper, we suggest that AD is a metabolic disease and that we should focus on metabolites that are affected by metabolic alterations to find effective therapeutics for AD...
May 2017: Yonsei Medical Journal
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