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Amyloid in blood

Yijun Pan, Jennifer L Short, Stephanie A Newman, Kwok H C Choy, Durgesh Tiwari, Christopher Yap, Danielle Senyschyn, William A Banks, Joseph A Nicolazzo
Epidemiological evidence suggests that people with bipolar disorder prescribed lithium exhibit a lower risk of Alzheimer's disease (AD) relative to those prescribed other mood-stabilizing medicines. Lithium chloride (LiCl) reduces brain β-amyloid (Aβ) levels, and the brain clearance of Aβ is reduced in AD. Therefore, the purpose of this study was to assess whether the cognitive benefits of LiCl are associated with enhanced brain clearance of exogenously-administered Aβ. The brain clearance of intracerebroventricularly (icv) administered125 I-Aβ42 was assessed in male Swiss outbred mice administered daily oral NaCl or LiCl (300 mg/kg for 21 days)...
March 12, 2018: Brain, Behavior, and Immunity
Ondrej Benek, Lukas Hroch, Laura Aitken, Frank Gunn-Moore, Lucie Vinklarova, Kamil Kuca, Daniel I Perez, Concepcion Perez, Ana Martinez, Zdenek Fisar, Kamil Musilek
Several neurodegenerative disorders including Alzheimer's disease (AD) have been connected with deregulation of casein kinase 1 (CK1) activity. Inhibition of CK1 therefore presents a potential therapeutic strategy against such pathologies. Recently, novel class of CK1-specific inhibitors with N-(benzo[d]thiazol-2-yl)-2-phenylacetamide structural scaffold has been discovered. 1-(benzo[d]thiazol-2-yl)-3-phenylureas, on the other hand, are known inhibitors amyloid-beta binding alcohol dehydrogenase (ABAD), an enzyme also involved in pathophysiology of AD...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Marianne Kaiser, Magdalena Jacobson, Pia Haubro Andersen, Poul Bækbo, José Joaquin Cerón, Jan Dahl, Damián Escribano, Stine Jacobsen
BACKGROUND: The pathogenesis of postpartum dysgalactia syndrome (PDS) in sows is not fully elucidated and affected sows often present vague clinical signs. Accurate and timely diagnosis is difficult, and PDS is often recognized with a delay once piglets begin to starve. Increased rectal temperature of the sow is an important diagnostic parameter, but it may also be influenced by a number of other parameters and is thus difficult to interpret. Inflammatory markers may be important adjuncts to the clinical assessment of sows with PDS, but such markers have only been studied to a limited extent...
March 12, 2018: BMC Veterinary Research
Frank J Simutis, Thomas P Sanderson, Gary D Pilcher, Michael J Graziano
The toxicity of avagacestat, a sulfonamide-based gamma (γ)-secretase inhibitor that was in development as a treatment for Alzheimer's disease, was evaluated in a comprehensive nonclinical toxicology program that included 6-month and 1-year repeat-dose toxicity studies in rats and dogs, respectively. There was a spectrum of mechanism-based changes attributed to inhibition of Notch signaling that regulates the differentiation and proliferation of cells throughout development and in adult tissues. In both rats and dogs, ovarian follicular degeneration and atrophy and a low incidence of granulosa cell hyperplasia and benign granulosa-thecal cell tumors were observed...
February 24, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Lirong Yan, Collin Y Liu, Koon-Pong Wong, Sung-Cheng Huang, Wendy J Mack, Kay Jann, Giovanni Coppola, John M Ringman, Danny J J Wang
Autosomal dominant Alzheimer's disease (ADAD) is a small subset of Alzheimer's disease that is genetically determined with 100% penetrance. It provides a valuable window into studying the course of pathologic processes that leads to dementia. Arterial spin labeling (ASL) MRI is a potential AD imaging marker that non-invasively measures cerebral perfusion. In this study, we investigated the relationship of cerebral blood flow measured by pseudo-continuous ASL (pCASL) MRI with measures of cerebral metabolism (FDG PET) and amyloid deposition (Pittsburgh Compound B (PiB) PET)...
2018: NeuroImage: Clinical
Chia-Liang Tsai, Jozef Ukropec, Barbara Ukropcová, Ming-Chyi Pai
Although exercise is an effective way to decrease the risk of developing Alzheimer's disease, the biological basis for such benefits from the different exercise modes remains elusive. The present study thus aimed (i) to investigate the effects of acute aerobic or resistance exercise on neurocognitive performances and molecular markers when performing a cognitive task involving executive functioning in older adults with amnestic mild cognitive impairment (aMCI), and (ii) to explore relationships of acute exercise-induced neurocognitive changes with changes in circulating levels of neuroprotective growth factors (e...
2018: NeuroImage: Clinical
Zhen Fan, Melanie Dani, Grazia D Femminella, Melanie Wood, Valeria Calsolaro, Mattia Veronese, Federico Turkheimer, Steve Gentleman, David J Brooks, Rainer Hinz, Paul Edison
PURPOSE: Neuroinflammation and microglial activation play an important role in amnestic mild cognitive impairment (MCI) and Alzheimer's disease. In this study, we investigated the spatial distribution of neuroinflammation in MCI subjects, using spectral analysis (SA) to generate parametric maps and quantify11 C-PBR28 PET, and compared these with compartmental and other kinetic models of quantification. METHODS: Thirteen MCI and nine healthy controls were enrolled in this study...
March 9, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Luca Bors, Kinga Tóth, Estilla Zsófia Tóth, Ágnes Bajza, Attila Csorba, Krisztián Szigeti, Domokos Máthé, Gábor Perlaki, Gergely Orsi, Gábor K Tóth, Franciska Erdő
Decreased beta-amyloid clearance in Alzheimer's disease and increased blood-brain barrier permeability in aged subjects have been reported in several articles. However, morphological and functional characterization of blood-brain barrier and its membrane transporter activity have not been described in physiological aging yet. The aim of our study was to explore the structural changes in the brain microvessels and possible functional alterations of P-glycoprotein at the blood-brain barrier with aging. Our approach included MR imaging for anatomical orientation in middle aged rats, electronmicroscopy and immunohistochemistry to analyse the alterations at cellular level, dual or triple-probe microdialysis and SPECT to test P-glycoprotein functionality in young and middle aged rats...
March 6, 2018: Brain Research Bulletin
Özlem Fentoğlu, Gözde Dinç, Atalay Doğru, Nermin Karahan, İlter İlhan, F Yeşim Kırzıoğlu, Mehmet Fatih Şentürk, Hikmet Orhan
BACKGROUND: There are no published studies regarding the role of the plasminogen (PLG) system in familial Mediterranean fever (FMF), FMF-associated secondary amyloidosis, or chronic periodontitis (CP), although recent limited data have focused on the association between FMF and chronic periodontitis. Therefore, the aim of this study was to evaluate the serum, salivary, and gingival tissue levels of PLG in patients with CP, FMF, and amyloidosis. METHODS: The study population included 122 patients with FMF (only FMF, and FMF and amyloidosis and 128 individuals who were systemically healthy controls...
February 21, 2018: Journal of Periodontology
Xinhua Zhan, Boryana Stamova, Frank R Sharp
This review proposes that lipopolysaccharide (LPS, found in the wall of all Gram-negative bacteria) could play a role in causing sporadic Alzheimer's disease (AD). This is based in part upon recent studies showing that: Gram-negative E. coli bacteria can form extracellular amyloid; bacterial-encoded 16S rRNA is present in all human brains with over 70% being Gram-negative bacteria; ultrastructural analyses have shown microbes in erythrocytes of AD patients; blood LPS levels in AD patients are 3-fold the levels in control; LPS combined with focal cerebral ischemia and hypoxia produced amyloid-like plaques and myelin injury in adult rat cortex...
2018: Frontiers in Aging Neuroscience
Simona Daniele, Daniela Frosini, Deborah Pietrobono, Lucia Petrozzi, Annalisa Lo Gerfo, Filippo Baldacci, Jonathan Fusi, Chiara Giacomelli, Gabriele Siciliano, Maria Letizia Trincavelli, Ferdinando Franzoni, Roberto Ceravolo, Claudia Martini, Ubaldo Bonuccelli
Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1-42 (Aβ1-42 ) and tau, in both brain and peripheral tissues. In addition to oligomers, the role of the interactions of α-syn with Aβ or tau has gradually emerged. Nevertheless, despite intensive research, NDs have no accepted peripheral markers for biochemical diagnosis. In this respect, Red Blood Cells (RBCs) are emerging as a valid peripheral model for the study of aging-related pathologies...
2018: Frontiers in Molecular Neuroscience
Guanshi Zhang, Elda Dervishi, Burim N Ametaj
The objective of this study was to search for potential alterations in innate immunity reactants and carbohydrate and lipid metabolism in the blood of transition dairy cows before, during, and after clinical occurrence of milk fever (MF) and identify potential predictive biomarkers of disease. One hundred pregnant multiparous Holstein dairy cows were involved in the study starting from -8wks before the expected day of parturition until +8wks postpartum as part of a large retrospective longitudinal study. Health status, DMI, milk yield, and milk composition were monitored during the whole experimental period...
March 5, 2018: Research in Veterinary Science
Tatyana Merkulova-Rainon, Chris S Mantsounga, Dong Broquères-You, Cristina Pinto, José Vilar, Diana Cifuentes, Philippe Bonnin, Nathalie Kubis, Daniel Henrion, Jean-Sébastien Silvestre, Bernard I Lévy
The pathophysiology of sporadic Alzheimer's disease (AD) remains uncertain. Along with brain amyloid-β (Aβ) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0...
March 7, 2018: Angiogenesis
Ling Li, Fan Zeng, Yu-Hui Liu, Hui-Yun Li, Shu-Yang Dong, Ze-Yan Peng, Yan-Jiang Wang, Hua-Dong Zhou
Polymorphisms of the cholesterol-24S-hydroxylase (CYP46A1) and apolipoprotein E (APOE) genes are risk factors for Alzheimer's disease (AD). Plasma level of 24S-hydroxcholesterol (24-OHC), the metabolite of cholesterol, is thought to correlate with AD. The present study investigated the correlation between these genetic factors and blood 24-OHC and amyloid-beta (Aβ) levels in AD patients. Association analysis, logistic regression, and linear regression were used to analyze the correlation of CYP46A1 and APOE genotypes with blood 24-OHC and Aβ levels and AD risk...
March 7, 2018: Molecular Neurobiology
Jonathan Vogelgsang, Jens Wiltfang, Hans W Klafki
The technical performance of immunological assays and their suitability for the intended use should be carefully validated before implementation in research, clinical studies or routine. We describe here the evaluation of a sandwich electrochemiluminescence immunoassay for measuring total Amyloid-β levels in human blood plasma as an example of a laboratory protocol for a partial "fit for purpose" assay performance validation. We tested two different assay protocols and addressed impact of sample dilution, parallelism, intra- and inter-assay variance, lower limit of quantification, lower limit of detection, and analytical spike recoveries...
2018: Methods in Molecular Biology
Zareen Amtul, Jun Yang, Simona Nikolova, Ting-Yim Lee, Robert Bartha, David F Cechetto
Defect in brain microperfusion is increasingly recognized as an antecedent event to Alzheimer's disease (AD) and ischemia. Nevertheless, studies on the role of impaired microperfusion as a pathological trigger to neuroinflammation, Aβ deposition as well as blood-brain barrier (BBB) disruption, and the etiological link between AD and ischemia are lacking. In this study, we employ in vivo sequential magnetic resonance imaging (MRI) and computed tomography (CT) imaging in a co-morbid rat model of β-amyloid toxicity (Aβ) and ischemia (ET1) with subsequent histopathology of striatal lesion core and penumbra at 1, 7, and 28 days post injury...
March 5, 2018: Molecular Neurobiology
D M Meléndez, S Marti, E A Pajor, D Moya, D Gellatly, E D Janzen, K S Schwartzkopf-Genswein
In Western-Canada, approximately half of the calves produced are castrated before 1 wk of age. Therefore, it is important to identify effective analgesic drugs to mitigate pain associated with castration and consequently improve animal welfare. The aim of this study was to assess the efficacy of a single s.c. dose of meloxicam at mitigating pain associated with knife and band castration in 1 wk old calves. Seventy-two Angus crossbred bull calves (47.3 ± 6.70 kg of BW, 1 wk old) were used in a 3 × 2 factorial design where main factors included castration method-sham (CT), band (BA) or knife (KN) castration-and medication-lactate ringer (NM) or 0...
February 28, 2018: Journal of Animal Science
Kathy Keyvani, Yvonne Münster, Nirup K Kurapati, Sebastian Rubach, Andreas Schönborn, Emre Kocakavuk, Mohamed Karout, Pia Hammesfahr, Ya-Chao Wang, Dirk M Hermann, Sarah Teuber-Hanselmann, Arne Herring
Women seem to have a higher vulnerability to Alzheimer's disease (AD), but the underlying mechanisms of this sex dichotomy are not well understood. Here, we first determined the influence of sex on various aspects of Alzheimer's pathology in transgenic CRND8 mice. We demonstrate that beta-amyloid (Aβ) plaque burden starts to be more severe around P180 (moderate disease stage) in female transgenics when compared to males and that aging aggravates this sex-specific difference. Further we show that female transgenics suffer from higher levels of neurovascular dysfunction around P180, resulting in impaired Aβ peptide clearance across the blood-brain-barrier at P360...
March 5, 2018: Brain Pathology
Natalia A Stefanova, Kseniya Yi Maksimova, Ekaterina A Rudnitskaya, Natalia A Muraleva, Nataliya G Kolosova
BACKGROUND: Cerebrovascular dysfunction plays a critical role in the pathogenesis of Alzheimer's disease (AD): the most common cause of dementia in the elderly. The involvement of neurovasculature disorders in the progression of AD is now increasingly appreciated, but whether they represent initial factors or late-stage pathological changes during the disease is unclear. Using senescence-accelerated OXYS rats, which simulate key characteristics of sporadic AD, we evaluated contributions of cerebrovascular alterations to the disease development...
February 9, 2018: BMC Genomics
Roberta Ghidoni, Rosanna Squitti, Mariacristina Siotto, Luisa Benussi
The criteria for the clinical diagnosis of AD include the analysis of biomarkers of the underlying brain disease pathology; a set of cerebrospinal fluid (CSF) tests, amyloid-β1-42 (Aβ42), total-tau (t-tau), and phosphorylated tau (p-tau), are available and their performance in a clinical setting has been assessed in several studies. Thus, in dementia research, great advances have been made in the discovery of putative biomarkers; however, disappointingly, few of them have been translated into clinically applicable assays...
February 28, 2018: Journal of Alzheimer's Disease: JAD
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