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https://www.readbyqxmd.com/read/28108398/association-between-butyrylcholinesterase-and-cerebrospinal-fluid-biomarkers-in-alzheimer-s-disease-patients
#1
António José Gabriel, Maria Rosário Almeida, Maria Helena Ribeiro, João Durães, Miguel Tábuas-Pereira, Ana Cristina Pinheiro, Rui Pascoal, Isabel Santana, Inês Baldeiras
The deficit of cholinergic activity is one of the main findings in Alzheimer's disease (AD), and is related to the synthesis of acetylcholine, and the hydrolysing enzymes, acetylcholinesterase and butyrylcholinesterase (BuChE). Together with the Apolipoprotein E-ε4 allele (ApoE-ε4), the BuChE-K variant has been proposed to increase AD risk in certain populations. In addition, this polymorphism has been associated with a lower capacity to attenuate β-amyloid aggregation. In the present study we explored the interaction of the BuChE-K variant with its activity in CSF, conventional AD biomarkers and ApoE genotype...
January 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28107809/plasma-protein-profiling-for-potential-biomarkers-in-the-early-diagnosis-of-alzheimer-s-disease
#2
Yuki Kitamura, Ryoko Usami, Sahoko Ichihara, Hirotaka Kida, Masayuki Satoh, Hidekazu Tomimoto, Mariko Murata, Shinji Oikawa
OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia in elderly persons. Since the pathology of AD develops slowly from a preclinical or early phase into a fully expressed clinical syndrome, at the time of diagnosis the disease has been progressing for many years. To facilitate the early diagnosis of AD, we performed protein profiling of blood in patients with mild AD as defined by the Functional Assessment Staging (FAST) scale. METHODS: Plasma samples from mild AD patients and healthy controls were analyzed using two-dimensional differential gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF/MS) followed by peptide mass fingerprinting...
January 20, 2017: Neurological Research
https://www.readbyqxmd.com/read/28107370/neuronal-injury-and-glial-changes-are-hallmarks-of-open-field-blast-exposure-in-swine-frontal-lobe
#3
Srinivasu Kallakuri, Alok Desai, Ke Feng, Sharvani Tummala, Tal Saif, Chaoyang Chen, Liying Zhang, John M Cavanaugh, Albert I King
With the rapid increase in the number of blast induced traumatic brain injuries and associated neuropsychological consequences in veterans returning from the operations in Iraq and Afghanistan, the need to better understand the neuropathological sequelae following exposure to an open field blast exposure is still critical. Although a large body of experimental studies have attempted to address these pathological changes using shock tube models of blast injury, studies directed at understanding changes in a gyrencephalic brain exposed to a true open field blast are limited and thus forms the focus of this study...
2017: PloS One
https://www.readbyqxmd.com/read/28106117/norovirus-p-particle-based-active-a%C3%AE-immunotherapy-elicits-sufficient-immunogenicity-and-improves-cognitive-capacity-in-a-mouse-model-of-alzheimer-s-disease
#4
Lu Fu, Yingnan Li, Yue Hu, Yayuan Zheng, Bin Yu, Haihong Zhang, Jiaxin Wu, Hui Wu, Xianghui Yu, Wei Kong
Disease-modifying immunotherapies focusing on reducing amyloid-beta (Aβ) deposition are the main treatment for Alzheimer's disease (AD). However, none of the Aβ immunotherapies has produced clinically meaningful results to date. The main reason for this lack of efficacy is that the vaccine induces insufficiently high antibody titers, as it contains small B-cell epitope of Aβ to avoid Aβ42-specific T-cell activation. With the aim of generating a potent AD vaccine, we designed the protein PP-3copy-Aβ1-6-loop123, comprising three copies of Aβ1-6 inserted into three loops of a novel vaccine platform, the norovirus P particle, which could present Aβ at its surface and remarkably enhance the immunogenicity of the vaccine...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102639/validation-of-an-mri-rating-scale-for-amyloid-related-imaging-abnormalities
#5
Arianne Bechten, Mike P Wattjes, Derk D Purcell, Esther Sanchez Aliaga, Marita Daams, H Robert Brashear, H Michael Arrighi, Frederik Barkhof
INTRODUCTION: Immunotherapeutic agents against amyloid beta (Aβ) are associated with adverse events, including amyloid-related imaging abnormalities with edema and effusion (ARIA-E). Recently, a magnetic resonance imaging (MRI) rating scale was developed for ARIA-E detection and classification. The aim of this study was to validate the use of this rating scale in a larger patient group with multiple raters. METHODS: MRI scans of 75 patients (29 with known ARIA-E and 46 control subjects) were analyzed by five neuroradiologists with different degrees of expertise, according to the ARIA-E rating scale...
January 19, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/28097205/impact-of-tau-and-amyloid-burden-on-glucose-metabolism-in-alzheimer-s-disease
#6
Gérard N Bischof, Frank Jessen, Klaus Fliessbach, Julian Dronse, Jochen Hammes, Bernd Neumaier, Oezguer Onur, Gereon R Fink, Juraj Kukolja, Alexander Drzezga, Thilo van Eimeren
In a multimodal PET imaging approach, we determined the differential contribution of neurofibrillary tangles (measured with [(18)F]AV-1451) and beta-amyloid burden (measured with [(11)C]PiB) on degree of neurodegeneration (i.e., glucose metabolism measured with [(18)F]FDG-PET) in patients with Alzheimer's disease. Across brain regions, we observed an interactive effect of beta-amyloid burden and tau deposition on glucose metabolism which was most pronounced in the parietal lobe. Elevated beta-amyloid burden was associated with a stronger influence of tau accumulation on glucose metabolism...
December 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28097089/selective-inhibition-of-phosphodiesterases-4-5-and-9-induces-hsp20-phosphorylation-and-attenuates-amyloid-beta-1-42-mediated-cytotoxicity
#7
Ryan T Cameron, Ellanor Whiteley, Jon P Day, Anna I Parachikova, George S Baillie
Phosphodiesterase (PDE) inhibitors are currently under evaluation as agents that may facilitate the improvement of cognitive impairment associated with Alzheimer's disease. Our aim was to determine whether inhibitors of PDEs 4, 5 and 9 could alleviate the cytotoxic effects of amyloid beta 1-42 (Aβ1-42) via a mechanism involving the small heatshock protein HSP20. We show that inhibition of PDEs 4, 5 and 9 but not 3 induces the phosphorylation of HSP20 which, in turn, increases the colocalisation between the chaperone and Aβ1-42 to significantly decrease the toxic effect of the peptide...
January 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28096464/functional-transformation-of-c-reactive-protein-by-hydrogen-peroxide
#8
Sanjay K Singh, Avinash Thirumalai, Asmita Pathak, Donald N Ngwa, Alok Agrawal
C-reactive protein (CRP) is present at sites of inflammation including amyloid plaques, atherosclerotic lesions and arthritic joints. CRP, in its native pentameric structural conformation, binds to cells and molecules which have exposed phosphocholine (PCh) groups. CRP, in its non-native pentameric structural conformation, binds to a variety of deposited, denatured and aggregated proteins, in addition to binding to PCh-containing substances. In this study, we investigated the effects of hydrogen peroxide (H2O2), a prototypical reactive oxygen species and which is also present at sites of inflammation, on the ligand recognition function of CRP...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096295/does-selection-for-short-sleep-duration-explain-human-vulnerability-to-alzheimer-s-disease
#9
Randolph M Nesse, Caleb E Finch, Charles L Nunn
Compared with other primates, humans sleep less and have a much higher prevalence of Alzheimer 's disease (AD) pathology. This article reviews evidence relevant to the hypothesis that natural selection for shorter sleep time in humans has compromised the efficacy of physiological mechanisms that protect against AD during sleep. In particular, the glymphatic system drains interstitial fluid from the brain, removing extra-cellular amyloid beta (eAβ) twice as fast during sleep. In addition, melatonin - a peptide hormone that increases markedly during sleep - is an effective antioxidant that inhibits the polymerization of soluble eAβ into insoluble amyloid fibrils that are associated with AD...
January 16, 2017: Evolution, Medicine, and Public Health
https://www.readbyqxmd.com/read/28094495/bacoside-a-an-indian-traditional-medicine-substance-inhibits-beta-amyloid-cytotoxicity-fibrillation-and-membrane-interactions
#10
Ravit Malishev, Shira Shaham-Niv, Sukhendu Nandi, Sofiya Kolusheva, Ehud Gazit, Raz Jelinek
Bacoside-A, a family of compounds extracted from the Bacopa monniera plant, is a folk-medicinal substance believed to exhibit therapeutic properties, particularly enhancing cognitive functions and improving memory. We show that bacoside-A exerted significant inhibitory effects upon cytotoxicity, fibrillation, and particularly membrane interactions of amyloid-beta (1-42) (Aβ42), the peptide playing a prominent role in Alzeheimer's disease progression and toxicity. Specifically, pre-incubation of bacoside-A with Aβ42 significantly reduced cell toxicity and inhibited fibril formation both in buffer solution and, more significantly, in the presence of membrane vesicles...
January 17, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28093977/the-amyloid-cascade-hypothesis-in-alzheimer-s-disease-it-s-time-to-change-our-mind
#11
Roberta Ricciarelli, Ernesto Fedele
Since its discovery in 1984, the beta amyloid peptide has treaded the boards of neurosciences as the star molecule in Alzheimer's disease pathogenesis. In the last decade, however, this vision has been challenged by evidence-based medicine showing the almost complete failure of clinical trials that experimented anti-amyloid therapies with great hopes. Moreover, data have accumulated which clearly indicates that this small peptide plays a key role in the physiological processes of memory formation. In the present review, we will discuss the different aspects of the amyloid cascade hypothesis, highlighting its pros and cons, and we will analyse the results of the therapeutic approaches attempted to date that should change the direction of Alzheimer's disease research in the future...
January 16, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28093567/beta-amyloid-sequelae-in-the-eye-a-critical-review-on-its-diagnostic-significance-and-clinical-relevance-in-alzheimer-s-disease
#12
REVIEW
T M Shah, S M Gupta, P Chatterjee, M Campbell, R N Martins
Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder. There is no test for its definitive diagnosis in routine clinical practice. Although phase III clinical trials have failed, only symptomatic treatment is currently available; a possible reason for these failed trials is that intervention commenced at an advanced stage of the disease. The hallmarks of an AD brain include plaques comprising of extracellular beta-amyloid (Aβ) protein aggregates and intracellular hyperphosphorylated neurofibrillary tangles of tau...
January 17, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28093254/risperidone-ameliorated-a%C3%AE-1-42-induced-cognitive-and-hippocampal-synaptic-impairments-in-mice
#13
Lingzhi Wu, Xiaowen Feng, Tingting Li, Baojuan Sun, Muhammad Zahid Khan, Ling He
Alzheimer's disease (AD) is a complex neurodegenerative disorder with cognitive impairment and major neuropathologic hallmark of amyloid-beta (Aβ) peptides. Risperidone, an atypical antipsychotic, can improve concentration and cognitive deficit in schizophrenia patients. In this study, behavior tests including Morris Water Maze test, Step-through passive avoidance test, Open Field test, Step-Down test, Hole-Board test and Novel object recognition test were preformed to examine the effect of Risperidone on Aβ1-42-induced cognitive dysfunction in both long-term and short-term memory...
January 13, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28089846/modulation-of-neuroinflammation-and-pathology-in-the-5xfad-mouse-model-of-alzheimer-s-disease-using-a-biased-and-selective-beta-1-adrenergic-receptor-partial-agonist
#14
Pooneh Memar Ardestani, Andrew K Evans, Bitna Yi, Tiffany Nguyen, Laurence Coutellier, Mehrdad Shamloo
Degeneration of noradrenergic neurons occurs at an early stage of Alzheimer's Disease (AD). The noradrenergic system regulates arousal and learning and memory, and has been implicated in regulating neuroinflammation. Loss of noradrenergic tone may underlie AD progression at many levels. We have previously shown that acute administration of a partial agonist of the beta-1 adrenergic receptor (ADRB1), xamoterol, restores behavioral deficits in a mouse model of AD. The current studies examined the effects of chronic low dose xamoterol on neuroinflammation, pathology, and behavior in the pathologically aggressive 5XFAD transgenic mouse model of AD...
January 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28079198/oligomerization-of-fvflm-peptides-and-their-ability-to-inhibit-beta-amyloid-peptides-aggregation-consideration-as-a-possible-model
#15
M Kouza, A Banerji, A Kolinski, I A Buhimschi, A Kloczkowski
Preeclampsia, a pregnancy-specific disorder, shares typical pathophysiological features with protein misfolding disorders including Alzheimer's disease. Characteristic for preeclampsia is the involvement of multiple proteins of which fragments of SERPINA1 and β-amyloid co-aggregate in urine and placenta of preeclamptic women. To explore the biophysical basis of this interaction, we investigated the multidimensional efficacy of the FVFLM sequence in SERPINA1, as a model inhibitory agent of β-amyloid aggregation...
January 12, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28078911/c5a-increases-the-injury-to-primary-neurons-elicited-by-fibrillar-amyloid-beta
#16
Michael X Hernandez, Pouya Namiranian, Eric Nguyen, Maria I Fonseca, Andrea J Tenner
C5aR1, the proinflammatory receptor for C5a, is expressed in the central nervous system on microglia, endothelial cells, and neurons. Previous work demonstrated that the C5aR1 antagonist, PMX205, decreased amyloid pathology and suppressed cognitive deficits in two Alzheimer's Disease (AD) mouse models. However, the cellular mechanisms of this protection have not been definitively demonstrated. Here, primary cultured mouse neurons treated with exogenous C5a show reproducible loss of MAP-2 staining in a dose-dependent manner within 24 hr of treatment, indicative of injury to neurons...
February 2017: ASN Neuro
https://www.readbyqxmd.com/read/28074940/alpha7-nicotinic-acetylcholine-receptor-is-required-for-amyloid-pathology-in-brain-endothelial-cells-induced-by-glycoprotein-120-methamphetamine-and-nicotine
#17
Liqun Liu, Jingyi Yu, Li Li, Bao Zhang, Lingjuan Liu, Chun-Hua Wu, Ambrose Jong, Ding-An Mao, Sheng-He Huang
One of the most challenging issues in HIV-associated neurocognitive disorders (HAND) caused by HIV-1 virotoxins and drug abuse is the lack of understanding the underlying mechanisms that are commonly associated with disorders of the blood-brain barrier (BBB), which mainly consists of brain microvascular endothelial cells (BMEC). Here, we hypothesized that Glycoprotein 120 (gp120), methamphetamine (METH) and nicotine (NT) can enhance amyloid-beta (Aβ) accumulation in BMEC through Alpha7 nicotinic acetylcholine receptor (α7 nAChR)...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28072821/maysin-and-its-flavonoid-derivative-from-centipedegrass-attenuates-amyloid-plaques-by-inducting-humoral-immune-response-with-th2-skewed-cytokine-response-in-the-tg-appswe-ps1de9-alzheimer-s-mouse-model
#18
Yuno Song, Hong-Duck Kim, Min-Kwon Lee, Il-Hwa Hong, Chung-Kil Won, Hyoung-Woo Bai, Seung Sik Lee, SungBeom Lee, Byung Yeoup Chung, Jae-Hyeon Cho
Alzheimer's disease (AD) is a slow, progressive neurodegenerative disease and the most common type of dementia in the elderly. The etiology of AD and its underlying mechanism are still not clear. In a previous study, we found that an ethyl acetate extract of Centipedegrass (CG) (i.e., EA-CG) contained 4 types of Maysin derivatives, including Luteolin, Isoorientin, Rhamnosylisoorientin, and Derhamnosylmaysin, and showed protective effects against Amyloid beta (Aβ) by inhibiting oligomeric Aβ in cellular and in vitro models...
2017: PloS One
https://www.readbyqxmd.com/read/28069541/a-bispecific-tribody-pet-radioligand-for-visualization-of-amyloid-beta-protofibrils-a-new-concept-for-neuroimaging
#19
Stina Syvänen, Xiaotian T Fang, Greta Hultqvist, Silvio R Meier, Lars Lannfelt, Dag Sehlin
Antibodies are highly specific for their target molecules, but their poor brain penetrance has restricted their use as PET ligands for imaging of targets within the CNS. The aim of this study was to develop an antibody-based radioligand, using the Tribody(TM) format, for PET imaging of soluble amyloid-beta (Aβ) protofibrils, which are suggested to cause neurodegeneration in Alzheimer's disease. Antibodies, even when expressed in smaller engineered formats, are large molecules that do not enter the brain in sufficient amounts for imaging purposes...
January 6, 2017: NeuroImage
https://www.readbyqxmd.com/read/28067349/the-synergistic-effect-between-klvff-and-self-assembly-chaperones-on-both-disaggregation-of-beta-amyloid-fibrils-and-reducing-consequent-toxicity
#20
Aoting Qu, Fan Huang, Ang Li, Huiru Yang, Hao Zhou, Jiafu Long, Linqi Shi
By combining KLVFF peptide and self-assembly chaperone we fabricate a new system to achieve the synchronization between Aβ fibril disaggregation and reducing toxicity of Aβ fragments (monomers or oligomers) that consequently formed. When the KLVFF peptides disaggregate fibrils into fragments, the hydrophobic domains of self-assembly chaperones promptly bind them at the same time. This binding blocks the re-aggregation of the fragments and their interaction with cells, and hence reduces the toxicity of these dangerous fragments...
January 19, 2017: Chemical Communications: Chem Comm
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