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https://www.readbyqxmd.com/read/28098992/mechanistic-insights-into-tunable-metal-mediated-hydrolysis-of-amyloid-%C3%AE-peptides
#1
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/28095900/post-stroke-dementia-a-comprehensive-review
#2
REVIEW
Milija D Mijajlović, Aleksandra Pavlović, Michael Brainin, Wolf-Dieter Heiss, Terence J Quinn, Hege B Ihle-Hansen, Dirk M Hermann, Einor Ben Assayag, Edo Richard, Alexander Thiel, Efrat Kliper, Yong-Il Shin, Yun-Hee Kim, SeongHye Choi, San Jung, Yeong-Bae Lee, Osman Sinanović, Deborah A Levine, Ilana Schlesinger, Gillian Mead, Vuk Milošević, Didier Leys, Guri Hagberg, Marie Helene Ursin, Yvonne Teuschl, Semyon Prokopenko, Elena Mozheyko, Anna Bezdenezhnykh, Karl Matz, Vuk Aleksić, DafinFior Muresanu, Amos D Korczyn, Natan M Bornstein
Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e...
January 18, 2017: BMC Medicine
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
#3
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/28093288/assessing-the-impact-of-lithium-chloride-on-the-expression-of-p-glycoprotein-at-the-blood-brain-barrier
#4
Stephanie A Newman, Yijun Pan, Jennifer L Short, Joseph A Nicolazzo
In addition to extruding drugs from the brain, P-glycoprotein (P-gp) at the blood-brain barrier (BBB) facilitates the brain-to-blood clearance of β-amyloid (Aβ) and is down-regulated in Alzheimer's disease (AD). Studies suggest that the mood-stabilising drug lithium exerts a protective effect against AD. While the mechanisms underlying this effect are not fully understood, evidence suggests that lithium chloride (LiCl) increases P-gp expression in vitro, albeit at concentrations substantially outside the therapeutic window...
January 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28087189/assessment-of-gapdh-expression-by-quantitative-real-time-pcr-in-blood-of-moroccan-ad-cases
#5
REVIEW
Nadia El Kadmiri, Meryam El Khachibi, Ilham Slassi, Bouchra El Moutawakil, Sellama Nadifi, Abdelaziz Soukri
INTRODUCTION: Neuroproteomics studies have showed the high affinity interactions between GAPDH - β-amyloid in Alzheimer disease. The aim of our study is to complete our previous studies by assessing the mechanism responsible of decreased expression of GAPDH protein in the blood of Moroccan AD cases probably due to an alteration at the transcriptional level or at the post translational level. METHODS: The mRNA expression of GAPDH was assessed by quantitative real time PCR in AD cases and healthy controls...
January 10, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
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
#6
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/28070499/metabolic-relationship-between-diabetes-and-alzheimer-s-disease-affected-by-cyclo-his-pro-plus-zinc-treatment
#7
REVIEW
Moon K Song, David S Bischoff, Albert M Song, Koichi Uyemura, Dean T Yamaguchi
BACKGROUND: Association of Alzheimer's Disease (AD) with Type 2 Diabetes (T2D) has been well established. Cyclo(His-Pro) plus zinc (Cyclo-Z) treatment ameliorated diabetes in rats and similar improvements have been seen in human patients. Treatment of amyloid precursor protein (APP) transgenic mice with Cyclo-Z exhibited memory improvements and significantly reduced Aβ-40 and Aβ-42 protein levels in the brain tissues of the mice. SCOPE OF REVIEW: Metabolic relationship between AD and T2D will be described with particular attention to insulin sensitivity and Aβ degradation in brain and plasma tissues...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28069541/a-bispecific-tribody-pet-radioligand-for-visualization-of-amyloid-beta-protofibrils-a-new-concept-for-neuroimaging
#8
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/28067167/6-benzothiazolyl-ureas-thioureas-and-guanidines-are-potent-inhibitors-of-abad-17%C3%AE-hsd10-and-potential-drugs-for-alzheimer-s-disease-treatment-design-synthesis-and-in-vitro-evaluation
#9
Ondrej Benek, Lukas Hroch, Laura Aitken, Rafael Dolezal, Patrick Guest, Marketa Benkova, Ondrej Soukup, Karel Musil, Kamil Kuca, Terry K Smith, Frank Gunn-Moore, Kamil Musilek
BACKGROUND: The mitochondrial enzyme amyloid beta-binding alcohol dehydrogenase (ABAD) also known as 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) has been connected with the pathogenesis of Alzheimer's disease (AD). ABAD/ 17β-HSD10 is a binding site for the amyloid-beta peptide (Aβ) inside the mitochondrial matrix where it exacerbates Aβ toxicity. Interaction between these two proteins triggers a series of events leading to mitochondrial dysfunction as seen in AD. METHODS: As ABAD's enzymatic activity is required for mediating Aβ toxicity, its inhibition presents a promising strategy for AD treatment...
January 9, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28064175/neuroimaging-of-inflammation-in-memory-and-related-other-disorders-nimrod-study-protocol-a-deep-phenotyping-cohort-study-of-the-role-of-brain-inflammation-in-dementia-depression-and-other-neurological-illnesses
#10
W Richard Bevan-Jones, Ajenthan Surendranathan, Luca Passamonti, Patricia Vázquez Rodríguez, Robert Arnold, Elijah Mak, Li Su, Jonathan P Coles, Tim D Fryer, Young T Hong, Guy Williams, Franklin Aigbirhio, James B Rowe, John T O'Brien
INTRODUCTION: Inflammation of the central nervous system is increasingly regarded as having a role in cognitive disorders such as dementia and depression, but it is not clear how such inflammation relates to other aspects of neuropathology, structural and functional changes in the brain and symptoms (as assessed via clinical and neuropsychological assessment and MRI). This study will explore these pathophysiological mechanisms using positron emission tomography (PET) which allows in vivo imaging of inflammation, amyloid and τ deposition, together with neuropsychological profiling, MRI and peripheral biomarker analysis...
January 7, 2017: BMJ Open
https://www.readbyqxmd.com/read/28061823/a-case-report-in-cardiovascular-magnetic-resonance-the-contrast-agent-matters-in-amyloid
#11
Marianna Fontana, Thomas A Treibel, Ana Martinez-Naharro, Stefania Rosmini, Raymond Y Kwong, Julian D Gillmore, Philip N Hawkins, James C Moon
BACKGROUND: Cardiac amyloidosis is a progressive but underdiagnosed and underappreciated cause of heart failure. In the last few years, cardiovascular magnetic resonance (CMR) has become the gold standard for non invasive diagnosis of cardiac amyloidosis with the characteristic subendocardial late gadolinium enhancement. CASE PRESENTATION: We describe a case of a patient who, in the process of aligning protocols for a trial between different centers, had a paired study with two different contrast agents, Dotarem® and MultiHance®...
January 7, 2017: BMC Medical Imaging
https://www.readbyqxmd.com/read/28061383/increased-blood-brain-barrier-permeability-is-associated-with-dementia-and-diabetes-but-not-amyloid-pathology-or-apoe-genotype
#12
Shorena Janelidze, Joakim Hertze, Katarina Nägga, Karin Nilsson, Christer Nilsson, Malin Wennström, Danielle van Westen, Kaj Blennow, Henrik Zetterberg, Oskar Hansson
Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls...
December 5, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28060355/longitudinal-in-vivo-imaging-of-the-cerebrovasculature-relevance-to-cns-diseases
#13
Margarita Arango-Lievano, Patrizia Giannoni, Sylvie Claeysen, Nicola Marchi, Freddy Jeanneteau
Remodeling of the brain vasculature is a common trait of brain pathologies. In vivo imaging techniques are fundamental to detect cerebrovascular plasticity or damage occurring overtime and in relation to neuronal activity or blood flow. In vivo two-photon microscopy allows the study of the structural and functional plasticity of large cellular units in the living brain. In particular, the thinned-skull window preparation allows the visualization of cortical regions of interest (ROI) without inducing significant brain inflammation...
December 6, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28059785/amylin-enhances-amyloid-%C3%AE-peptide-brain-to-blood-efflux-across-the-blood-brain-barrier
#14
Loqman A Mohamed, Haihao Zhu, Youssef M Mousa, Erming Wang, Wei Qiao Qiu, Amal Kaddoumi
Findings from Alzheimer's disease (AD) mouse models showed that amylin treatment improved AD pathology and enhanced amyloid-β (Aβ) brain to blood clearance; however, the mechanism was not investigated. Using the Tg2576 AD mouse model, a single intraperitoneal injection of amylin significantly increased Aβ serum levels, and the effect was abolished by AC253, an amylin receptor antagonist, suggesting that amylin effect could be mediated by its receptor. Subsequent mechanistic studies showed amylin enhanced Aβ transport across a cell-based model of the blood-brain barrier (BBB), an effect that was abolished when the amylin receptor was inhibited by two amylin antagonists and by siRNA knockdown of amylin receptor Ramp3...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28058581/the-role-of-autophagy-in-the-correlation-between-neuron-damage-and-cognitive-impairment-in-rat-chronic-cerebral-hypoperfusion
#15
Wenying Zou, Yufei Song, Yumei Li, Yu Du, Xiaojie Zhang, Jiangliang Fu
Pathological changes and cognitive impairment caused by chronic cerebral hypoperfusion (CCH) have been previously reported. However, how these changes progress remains unclear. Additionally, there are few studies regarding the mechanism underlying the involvement of autophagy in these processes. Two-step bilateral common carotid artery occlusion (BCCAO) was performed to replicate CCH in Sprague Dawley rats. The animals were divided into seven groups, including a sham group and 2-, 4-, 8-, 12-, 16-, and 20-week BCCAO groups (n = 7 per group)...
January 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28045978/cord-blood-acute-phase-reactants-predict-early-onset-neonatal-sepsis-in-preterm-infants
#16
Leena B Mithal, Hannah L Palac, Ram Yogev, Linda M Ernst, Karen K Mestan
BACKGROUND: Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection. METHODS: In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7-32...
2017: PloS One
https://www.readbyqxmd.com/read/28045249/rationally-designed-peptides-and-peptidomimetics-as-inhibitors-of-amyloid-%C3%AE-a%C3%AE-aggregation-potential-therapeutics-of-alzheimer-s-disease
#17
Deepti Goyal, Suniba Shuaib, Sukhmani Mann, Bhupesh Goyal
Alzheimer's disease (AD) is a progressive neurodegenerative disease with no clinically accepted treatment to cure or halt its progression. The worldwide effort to develop peptide-based inhibitors of amyloid-β (Aβ) aggregation can be considered an unplanned combinatorial experiment. An understanding of what has been done and achieved may advance our understanding of AD pathology and the discovery of effective therapeutic agents. We review here the history of such peptide-based inhibitors, including those based on the Aβ sequence and those not derived from that sequence, containing both natural and unnatural amino acid building blocks...
January 18, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28041733/glucose-requirements-of-an-activated-immune-system-in-lactating-holstein-cows
#18
S K Kvidera, E A Horst, M Abuajamieh, E J Mayorga, M V Sanz Fernandez, L H Baumgard
Accurately quantifying activated immune system energy requirements in vivo is difficult, but a better understanding may advance strategies to maximize animal productivity. Study objectives were to estimate whole-body glucose utilization following an i.v. endotoxin challenge. Lactating Holstein cows were jugular catheterized and assigned 1 of 3 bolus treatments: control (CON; 5 mL of saline; n = 6), lipopolysaccharide (LPS)-administered (LPS-C; 1.5 μg/kg of body weight; Escherichia coli 055:B5; n = 6), and LPS + euglycemic clamp (LPS-Eu; 1...
December 29, 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/28040512/extracellular-vesicles-of-the-blood-brain-barrier-role-in-the-hiv-1-associated-amyloid-beta-pathology
#19
Ibolya E András, Ana Leda, Marta Garcia Contreras, Luc Bertrand, Minseon Park, Marta Skowronska, Michal Toborek
HIV-infected brains are characterized by increased amyloid beta (Aβ) deposition. It is believed that the blood-brain barrier (BBB) is critical for Aβ homeostasis and contributes to Aβ accumulation in the brain. Extracellular vesicles (ECV), like exosomes, recently gained a lot of attention as potentially playing a significant role in Aβ pathology. In addition, HIV-1 hijacks the exosomal pathway for budding and release. Therefore, we investigated the involvement of BBB-derived ECV in the HIV-1-induced Aβ pathology in the brain...
December 29, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28039950/ageing-causes-prominent-neurovascular-dysfunction-associated-with-loss-of-astrocytic-contacts-and-gliosis
#20
Jessica Duncombe, Ross J Lennen, Maurits A Jansen, Ian Marshall, Joanna M Wardlaw, Karen Horsburgh
AIMS: Normal neurovascular coupling, mediated by the fine interplay and communication of cells within the neurovascular unit, is critical for maintaining normal brain activity and cognitive function. This study investigated whether, with advancing age there is disruption of neurovascular coupling and specific cellular components of the neurovascular unit, and whether the effects of increasing amyloid (a key feature of Alzheimer's disease) would exacerbate these changes. METHODS: Wild-type mice, in which amyloid deposition is absent, were compared to transgenic APP littermates (TgSwDI) which develop age-dependent increases in amyloid...
December 31, 2016: Neuropathology and Applied Neurobiology
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