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Peter Nilsson, Marcus Bäck, Hanna Appelqvist, Harry LeVine
Deposits comprised of amyloid-β(Aβ) are one of the pathological hallmarks of Alzheimer's disease (AD) and small hydrophobic ligands targeting these aggregated species are used clinically for diagnosis of AD. Herein, we observed that anionic oligothiophenes efficiently displaced X-34, a Congo Red analogue, but not Pittsburgh compound B (PIB) from recombinant Aβ amyloid fibrils and Alzheimer's disease brain-derived Aβ. Overall, we foresee that the oligothiophene scaffold offers the possibility to develop novel high-affinity ligands for Aβ pathology only found in human AD brain, targeting a different site than PIB...
October 21, 2016: Chemistry: a European Journal
Xiaotian T Fang, Jonas Eriksson, Gunnar Antoni, Ulrika Yngve, Linda Cato, Lars Lannfelt, Dag Sehlin, Stina Syvänen
Alzheimer's disease (AD) is characterized by aggregation of amyloid beta (Aβ) into insoluble plaques. Intermediates, Aβ oligomers (Aβo), appear to be the mechanistic cause of disease. The de facto PET AD ligand, [(11)C]PIB, binds and visualizes Aβ plaque load, which does not correlate well with disease severity. Therefore, finding a dynamic target that changes with pathology progression in AD is of great interest. Aβo alter synaptic plasticity, inhibit long-term potentiation, and facilitate long-term depression; key mechanisms involved in memory and learning...
October 12, 2016: Neuropharmacology
Rajendran Senthil Kumar, Chin-Hui Shen, Pei-Yin Wu, Subbiah Suresh Kumar, Moda Sang Hua, Kai-Wun Yeh
In Oncidium, redox homeostasis involved in flowering is mainly due to ascorbic acid (AsA). Here, we discovered that Oncidium floral repression is caused by an increase in AsA-mediated NO levels, which is directed by the enzymatic activities of nitrate reductase (NaR) and nitrite reducatase (NiR). Through Solexa transcriptomic analysis of two libraries, 'pseudobulb with inflorescent bud' (PIB) and 'pseudobulb with axillary bud' (PAB), we identified differentially expressed genes related to NO metabolism. Subsequently, we showed a significant reduction of NaR enzymatic activities and NO levels during bolting and blooming stage, suggesting that NO controlled the phase transition and flowering process...
October 12, 2016: Scientific Reports
Mary M Machulda, Clint E Hagen, Heather J Wiste, Michelle M Mielke, David S Knopman, Rosebud O Roberts, Prashanthi Vemuri, Val J Lowe, Clifford R Jack, Ronald C Petersen
OBJECTIVE: The objective of this study was to examine practice effects and longitudinal cognitive change in 190 clinically normal elderly classified according to a two-feature biomarker model for Alzheimer's disease. METHODS: All participants completed neuropsychological testing, MRI, FDG-PET, and PiB-PET at their baseline evaluation. We divided participants into four groups based on neuroimaging measures of amyloid (A+ or A-) and neurodegeneration (N+ or N-) and reexamined cognition at 15- and 30-month intervals...
October 11, 2016: Clinical Neuropsychologist
Yasuhiko Ikari, Go Akamatsu, Tomoyuki Nishio, Kenji Ishii, Kengo Ito, Takeshi Iwatsubo, Michio Senda
BACKGROUND: While fluorodeoxyglucose (FDG) and amyloid PET is valuable for patient management, research, and clinical trial of therapeutics on Alzheimer's disease, the specific details of the PET scanning method including the PET camera model type influence the image quality, which may further affect the interpretation of images and quantitative capabilities. To make multicenter PET data reliable and to establish PET scanning as a universal diagnostic technique and a verified biomarker, we have proposed phantom test procedures and criteria for optimizing image quality across different PET cameras...
December 2016: EJNMMI Physics
Xiaoli Pan, Zhichun Chen, Guoqiang Fei, Shumei Pan, Weiqi Bao, Shuhua Ren, Yihui Guan, Chunjiu Zhong
To date, we still lack disease-modifying therapies for Alzheimer's disease (AD). Here, we report that long-term administration of benfotiamine improved the cognitive ability of patients with AD. Five patients with mild to moderate AD received oral benfotiamine (300 mg daily) over 18 months. All patients were examined by positron emission tomography with Pittsburgh compound B (PiB-PET) and exhibited positive imaging with β-amyloid deposition, and three received PiB-PET imaging at follow-up. The five patients exhibited cognitive improvement as assayed by the Mini-Mental Status Examination (MMSE) with an average increase of 3...
October 1, 2016: Neuroscience Bulletin
María Julieta Russo, Gabriela Cohen, Patricio Chrem Mendez, Jorge Campos, Federico E Nahas, Ezequiel I Surace, Silvia Vazquez, Deborah Gustafson, Salvador Guinjoan, Ricardo F Allegri, Gustavo Sevlever
PURPOSE: Argentina-Alzheimer's Disease Neuroimaging Initiative (Arg-ADNI) is the first ADNI study to be performed in Latin America at a medical center with the appropriate infrastructure. Our objective was to describe baseline characteristics and to examine whether biomarkers related to Alzheimer's disease (AD) physiopathology were associated with worse memory performance. PATIENTS AND METHODS: Fifteen controls and 28 mild cognitive impairment and 13 AD dementia subjects were included...
2016: Neuropsychiatric Disease and Treatment
Ruiqing Ni, Per-Göran Gillberg, Nenad Bogdanovic, Matti Viitanen, Liisa Myllykangas, Inger Nennesmo, Bengt Långström, Agneta Nordberg
INTRODUCTION: Amyloid imaging has been integrated into diagnostic criteria for Alzheimer's disease (AD). How amyloid tracers binding differ for different tracer structure and amyloid-β aggregate in autosomal dominant AD (ADAD) and sporadic AD is unclear. METHODS: Binding properties of different amyloid tracers were examined in brain homogenates from six ADAD with APPswe, PS1 M146V, and PS1 EΔ9 mutations, 13 sporadic AD, and 14 control cases. RESULTS: (3)H-PIB, (3)H-florbetaben, (3)H-AZD2184, and BTA-1 shared a high- and a varying low-affinity binding site in the frontal cortex of sporadic AD...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Laure Saint-Aubert, Ove Almkvist, Konstantinos Chiotis, Rita Almeida, Anders Wall, Agneta Nordberg
BACKGROUND: The recent development of tau-specific positron emission tomography (PET) tracers has allowed in vivo quantification of regional tau deposition and offers the opportunity to monitor the progression of tau pathology along with cognitive impairment. In this study, we investigated the relationships of cerebral tau deposition ([(18)F]THK5317-PET) and metabolism ([(18)F]FDG-PET) with concomitant cognitive function in patients with probable Alzheimer's disease (AD). METHODS: Nine patients diagnosed with AD dementia and 11 with prodromal AD (mild cognitive impairment, amyloid-positive on [(11)C]PiB-PET) were included in this study...
September 29, 2016: Alzheimer's Research & Therapy
Qu Tian, Susan M Resnick, Murat Bilgel, Dean F Wong, Luigi Ferrucci, Stephanie A Studenski
BACKGROUND: Motor slowing is associated with risk of Alzheimer's disease. Whether β-amyloid (Aβ) burden is associated with motor decline, independent of cognitive decline, is unknown. METHODS: About 59 cognitively unimpaired older participants had baseline PET-PiB scans and repeated measures of lower (usual gait speed, 400-m time, Health ABC Physical Performance Battery (HABCPPB) score, total standing balance time) and upper (mean tapping time) extremity performance during a mean follow-up of 4...
September 24, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Ozan Ayhan, Thomas Eckert, Felix A Plamper, Holger Helten
The significance of inorganic main-group polymers is demonstrated most clearly by the commercial relevance of polysiloxanes (silicones). Organoboron-based materials such as π-conjugated organoborane polymers and BN-doped polycyclic aromatic hydrocarbons are currently attracting considerable attention. Surprisingly, poly(iminoborane)s (PIBs; [BRNR']n ), that is, the parent unsaturated BN polymers, which are formally isoelectronic to polyacetylene, have not been convincingly characterized thus far. Herein, we present the synthesis and comprehensive characterization of a linear oligo(iminoborane), which comprises a chain of 12-14 BN units on average...
October 10, 2016: Angewandte Chemie
Clemens Schroeder, Min Tae M Park, Jürgen Germann, M Mallar Chakravarty, Lars Michels, Spyros Kollias, Sara L Kroll, Alfred Buck, Valerie Treyer, Egemen Savaskan, Paul G Unschuld, Roger M Nitsch, Andrea M Kälin, Christoph Hock, Anton F Gietl, Sandra E Leh
Aβ deposition is a driving force of Alzheimer's disease pathology and can be detected early by amyloid positron emission tomography. Identifying presymptomatic structural brain changes associated with Aβ deposition might lead to a better understanding of its consequences and provide early diagnostic information. In this respect we analyzed measures of cortical thickness and subcortical volumes along with hippocampal, thalamic and striatal shape and surface area by applying novel analysis strategies for structural magnetic resonance imaging...
September 20, 2016: European Journal of Neuroscience
Björn Pilebro, Sandra Arvidsson, Per Lindqvist, Torbjörn Sundström, Per Westermark, Gunnar Antoni, Ole Suhr, Jens Sörensen
BACKGROUND: DPD scintigraphy has been advocated for imaging cardiac amyloid in ATTR amyloidosis. PET utilizing (11)C-Pittsburgh compound B (PIB) is the gold standard for imaging brain amyloid in Alzheimer's disease. PIB was recently shown to identify cardiac amyloidosis in both AL and ATTR amyloidosis. In the ATTR population, two types of amyloid fibrils exist, one containing fragmented and full-length TTR (type A) and the other only full-length TTR (type B). The aim of this study was to further evaluate PIB-PET in patients with hereditary ATTR amyloidosis...
September 19, 2016: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
Keisuke Matsubara, Masanobu Ibaraki, Hitoshi Shimada, Yoko Ikoma, Tetsuya Suhara, Toshibumi Kinoshita, Hiroshi Ito
High non-specific uptake of [(11)C]Pittsburgh compound B ([(11)C]PiB) in white matter and signal spillover from white matter, due to partial volume effects, confound radioactivity measured in positron emission tomography (PET) with [(11)C]PiB. We aimed to reveal the partial volume effect in absolute values of kinetic parameters for [(11)C]PiB, in terms of spillover from white matter. Dynamic data acquired in [(11)C]PiB PET scans with five healthy volunteers and eight patients with Alzheimer's disease were corrected with region-based and voxel-based partial volume corrections...
September 14, 2016: NeuroImage
Adrian Wong, Alexander Y L Lau, Jie Yang, Zhaolu Wang, Wenyan Liu, Bonnie Y K Lam, Lisa Au, Lin Shi, Defeng Wang, Winnie C W Chu, Yun-Yun Xiong, Eugene S K Lo, Lorraine S N Law, Thomas W H Leung, Linda C W Lam, Anne Y Y Chan, Yannie O Y Soo, Eric Y L Leung, Lawrence K S Wong, Vincent C T Mok
BACKGROUND: The objectives of this study are 1) to examine the frequencies of neuropsychiatric symptom clusters in patients with stroke or transient ischemic attack (TIA) by cognitive level and stroke subtype; and 2) to evaluate effect of demographic, clinical, and neuroimaging measures of chronic brain changes and amyloid upon neuropsychiatric symptom clusters. METHODS: Hospital-based, cross-sectional study. 518 patients were administered the Neuropsychiatric Inventory (NPI) 3-6 months post index admission...
2016: PloS One
Yeo Jin Kim, Hee Jin Kim, Jae-Hyun Park, Seonwoo Kim, Sook-Young Woo, Ki-Chang Kwak, Jong Min Lee, Na-Yeon Jung, Jae Seung Kim, Yearn Seong Choe, Kyung-Han Lee, Seung Hwan Moon, Jae-Hong Lee, Yun Joong Kim, David J Werring, Duk L Na, Sang Won Seo
OBJECTIVE: To determine whether amyloid and hypertensive cerebral small vessel disease (hCSVD) changes synergistically affect the progression of lobar microbleeds in patients with subcortical vascular mild cognitive impairment (svMCI). METHODS: Among 72 patients with svMCI who underwent brain MRI and [(11)C] Pittsburgh compound B (PiB)-PET, 52 (72.2%) completed the third year of follow-up. These patients were evaluated by annual neuropsychological testing, brain MRI, and follow-up PiB-PET...
October 11, 2016: Neurology
M Edip Gurol, J Alex Becker, Panagiotis Fotiadis, Grace Riley, Kristin Schwab, Keith A Johnson, Steven M Greenberg
OBJECTIVE: We hypothesized that florbetapir, a Food and Drug Administration-approved PET tracer, could distinguish cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (ICH) from hypertensive ICH (HTN-ICH). METHODS: We prospectively enrolled survivors of primary ICH related to probable CAA (per Boston Criteria, n = 10) and HTN-ICH (n = 9) without dementia. All patients underwent florbetapir-PET and multimodal MRI, and patients with CAA had additional Pittsburgh compound B (PiB) PET...
September 7, 2016: Neurology
Tor S Clemmensen, Henning Mølgaard, Niels F Andersen, Steen Baerentzen, Jens Soerensen, Steen H Poulsen
The present case illustrates the diagnostic challenges in symptomatic patients with heart failure of unknown etiology. The patients were previously diagnosed with κ-light chain amyloidosis without cardiac involvement. Echocardiography showed heart failure with mildly reduced ejection fraction but no signs of amyloidosis. Coronary angiogram showed normal arteries and 11C-PIB positron emission tomography was negative for amyloid deposits. Exercise testing revealed severe heart failure and reduced coronary flow velocity reserve...
September 7, 2016: Echocardiography
Annie M Racine, Lindsay R Clark, Sara E Berman, Rebecca L Koscik, Kimberly D Mueller, Derek Norton, Christopher R Nicholas, Kaj Blennow, Henrik Zetterberg, Bruno Jedynak, Murat Bilgel, Cynthia M Carlsson, Bradley T Christian, Sanjay Asthana, Sterling C Johnson
It is not known whether computerized cognitive assessments, like the CogState battery, are sensitive to preclinical cognitive changes or pathology in people at risk for Alzheimer's disease(AD). In 469 late middle-aged participants from the Wisconsin Registry for Alzheimer's Prevention(mean age 63.8±7 years at testing; 67% female; 39% APOE4+), we examined relationships between a CogState abbreviated battery(CAB) of seven tests and demographic characteristics, traditional paper-based neuropsychological tests as well as a composite cognitive impairment index, cognitive impairment status(determined by consensus review), and biomarkers for amyloid and tau(CSF phosphorylated-tau/Aβ42 and global PET-PiB burden) and neural injury(CSF neurofilament light protein)...
October 18, 2016: Journal of Alzheimer's Disease: JAD
Grzegorz Gralewicz, Grzegorz Owczarek, Janusz Kubrak
This article presents a comparison of the test results of selected mechanical parameters (hardness, Young's modulus, critical force for delamination) for protective filters intended for eye protection against harmful infrared radiation. Filters with reflective metallic films were studied, as well as interference filters developed at the Central Institute for Labour Protection - National Research Institute (CIOP-PIB). The test results of the selected mechanical parameters were compared with the test results, conducted in accordance with a standardised method, of simulating filter surface destruction that occurs during use...
October 6, 2016: International Journal of Occupational Safety and Ergonomics: JOSE
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