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Al amyloid

Eline T S van Maanen, Tamara S van Steeg, Maurice Ahsman, Maria S Michener, Mary J Savage, Matthew E Kennedy, Huub J Kleijn, Julie A Stone, Meindert Danhof
The abnormal accumulation of amyloid-β (Aβ) in the brain parenchyma has been posited as a central event in the pathophysiology of Alzheimer's disease. Recently, we have proposed a systems pharmacology model of the APP pathway, describing the Aβ precursor protein (APP) metabolite responses (Aβ40, Aβ42, sAPPα and sAPPβ) to β-secretase 1 (BACE1) inhibition (van Maanen et al., 2016). In this investigation this model was challenged to describe Aβ dynamics following γ-secretase (GS) inhibition. This led an extended systems pharmacology model, with separate descriptions to characterize the sequential cleavage steps of APP by BACE1 and GS, to describe the differences in Aβ response to their respective inhibition...
March 21, 2018: Journal of Pharmacology and Experimental Therapeutics
Jessica Alber, Kelly McGarry, Richard B Noto, Peter J Snyder
Background: Recent genome-wide association screening (GWAS) studies have linked Alzheimer's disease (AD) neuropathology to gene networks that regulate immune function. Kan et al. recently reported that Arg1 (an anti-inflammatory gene that codes for arginase-1) is expressed in parts of the brain associated with amyloidosis prior to the onset of neuronal loss, suggesting that chronic brain arginine deprivation promotes AD-related neuropathology. They blocked arginine catabolism in their mouse AD model by administration of eflornithine (DFMO) to juvenile animals, effectively blocking the expression of AD-related amyloid pathology as the mice aged...
2018: Frontiers in Aging Neuroscience
Joshua T Byers, Xin Qing, Christopher Lo, Samuel W French, Ping Ji
Amyloidosis is a disorder characterized by the deposition of insoluble abnormal proteins in the extracellular space. It may occur as a localized lesion or as a systemic disease involving multiple organs and systems. Localized conjunctival amyloidosis is rare and is less frequently associated with systemic involvement. Although amyloidosis itself is a benign lesion involvement of multiple organs and systems is associated with poor prognosis. Diagnosis of amyloidosis is made on biopsy specimens with Congo red staining for the appearance of apple-green birefringence under polarized light microscopy...
March 15, 2018: Experimental and Molecular Pathology
E A Horst, S K Kvidera, E J Mayorga, C S Shouse, M Al-Qaisi, M J Dickson, J Ydstie, H A Ramirez Ramirez, A F Keating, D J Dickson, K E Griswold, L H Baumgard
Activated immune cells are insulin sensitive and utilize copious amounts of glucose. Because chromium (Cr) increases insulin sensitivity and may be immunomodulatory, our objective was to evaluate the effect of supplemental Cr (KemTrace Cr propionate, 20 g/d; Kemin Industries Inc., Des Moines, IA) on immune system glucose utilization and immune system dynamics following an intravenous endotoxin challenge in lactating Holstein cows. Twenty cows (320 ± 18 d in milk) were randomly assigned to 1 of 4 treatments: (1) pair-fed (PF) control (PF-CON; 5 mL of saline; n = 5), (2) PF and Cr supplemented (PF-Cr; 5 mL of saline; n = 5), (3) lipopolysaccharide (LPS)-euglycemic clamp and control supplemented (LPS-CON; 0...
March 14, 2018: Journal of Dairy Science
Paolo Milani, Giampaolo Merlini, Giovanni Palladini
Light chain (AL) amyloidosis is caused by a usually small plasma-cell clone that is able to produce the amyloidogenic light chains. They are able to misfold and aggregate, deposit in tissues in the form of amyloid fibrils and lead to irreversible organ dysfunction and eventually death if treatment is late or ineffective. Cardiac damage is the most important prognostic determinant. The risk of dialysis is predicted by the severity of renal involvement, defined by the baseline proteinuria and glomerular filtration rate, and by the response to therapy...
2018: Mediterranean Journal of Hematology and Infectious Diseases
Wengen Chen, Van-Khue Ton, Vasken Dilsizian
PURPOSE OF REVIEW: The two most common types of cardiac amyloidosis are caused by fibril deposits of immunoglobulin light chains (AL) and transthyretin (TTR), each with distinct prognosis and clinical management. Cardiac amyloidosis is under-recognized among heart failure patients with preserved ejection fraction (HFpEF). Bone-seeking tracers like99m Tc-PYP and99m Tc-DPD have long been used to identify cardiac amyloidosis, and more recently, to differentiate TTR from AL cardiac amyloidosis in symptomatic patients...
March 8, 2018: Current Cardiology Reports
Joe Udeochu, Faten A Sayed, Li Gan
Mutations in TREM2 increase risk for late-onset AD. In this issue of Neuron, Zhao et al. (2018) show that TREM2 binds Aβ to enhance its clearance and Lee et al. (2018) demonstrate that human TREM2 expression in AD mice ameliorates Aβ-associated deficits.
March 7, 2018: Neuron
Liying Yang, Hongyan Wang, Lijun Liu, Anmu Xie
Dementia, a condition that frequently afflicts patients in advanced stages of Parkinson's disease (PD), results in decreased quality of life and survival time. Nevertheless, the pathological mechanisms underlying Parkinson's disease dementia (PDD) are not completely understood. The symptoms characteristic of PDD may be the result of functional and structural deficiencies. The present study implicates the accumulation of Lewy bodies in the cortex and limbic system as a potent trigger in the development of PDD...
2018: Frontiers in Neuroscience
A V Finkelstein, N V Dovidchenko, O V Galzitskaya
Meisl et al. have recently observed an anomalous dependence of the amyloid formation rate on the protein concentration. A novel mechanism of fibril growth has been proposed by Meisl et al. to explain the abnormality; it consists in the fibril-catalyzed initiation of fibril formation with saturation of catalytic sites at high concentrations of substrates. Our article describes an alternative explanation of the anomalous kinetics, assuming that the formation of metastable oligomers competes with fibril formation by decreasing the concentration of free monomers...
January 2018: Molekuliarnaia Biologiia
Norman C Charles, Irina Belinsky, Habeeb Ahmad
Conjunctival amyloid is usually of the immunoglobulin light chain (AL) variety. The authors report an exceptional case of bilateral limbal amyloid deposits that were identified by mass spectrometry as keratin-related specifically regarding to basal keratinocyte keratins 5 and 14. Cytokeratin-related amyloid has been described by immunohistochemical analysis of formalin-fixed cutaneous and mucous membrane lesions but not ocular tissues. The conjunctival lesion in the right eye contained intraepithelial dyskeratotic cells that extended to the surface, causing a lacy leukoplakia on clinical examination...
March 2, 2018: Ophthalmic Plastic and Reconstructive Surgery
Jason A Chen, Scott C Fears, Anna J Jasinska, Alden Huang, Noor B Al-Sharif, Kevin E Scheibel, Thomas D Dyer, Anne M Fagan, John Blangero, Roger Woods, Matthew J Jorgensen, Jay R Kaplan, Nelson B Freimer, Giovanni Coppola
Background: The Caribbean vervet monkey ( Chlorocebus aethiops sabaeus ) is a potentially valuable animal model of neurodegenerative disease. However, the trajectory of aging in vervets and its relationship to human disease is incompletely understood. Methods: To characterize biomarkers associated with neurodegeneration, we measured cerebrospinal fluid (CSF) concentrations of Aβ1-40 , Aβ1-42 , total tau, and p-tau181 in 329 members of a multigenerational pedigree...
February 2018: Brain and Behavior
Hassan Alyami, Emad Al-Osail, Shawgi Harbi, Mohammed Bu Bshait
INTRODUCTION: Benign Osseous metaplasia of the breast is rare, with only a few cases reported in the literature. Here we present a case of benign osseous metaplasia of the breast presenting as a breast lump. CASE PRESENTATION: 38-year-old previously well woman presented with a one-year history of bilateral breast pain and a left-sided breast lump. Ultrasound and mammography suggested calcified fibroadenoma. An ultrasound-guided true cut biopsy revealed fibrous tissue containing foci of adenosis in the presence of a myoepithelial cell layer...
February 19, 2018: International Journal of Surgery Case Reports
Nobuaki Egashira, Yuki Akiyoshi, Hikari Iba, Takashi Arai, Izzettin Hatip-Al-Khatib, Kenichi Mishima, Katsunori Iwasaki
Previously, we reported that ovariectomy (OVX) combined with β-amyloid peptide (Aβ) impaired spatial memory by decreasing extracellular acetylcholine (ACh) levels in the dorsal hippocampus. Here, we investigated the effect of tokishakuyakusan (TSS), a Kampo medicine, on the impairment of spatial memory induced by OVX combined with Aβ in rats. Repeated administration of TSS (300 mg/kg, p.o.) significantly decreased the number of errors in the eight-arm radial maze test. Though TSS had no effect on extracellular ACh levels at baseline, TSS significantly increased extracellular ACh levels in the dorsal hippocampus...
February 8, 2018: Journal of Pharmacological Sciences
Jaeyoon Chung, Xiaoling Zhang, Mariet Allen, Xue Wang, Yiyi Ma, Gary Beecham, Thomas J Montine, Steven G Younkin, Dennis W Dickson, Todd E Golde, Nathan D Price, Nilüfer Ertekin-Taner, Kathryn L Lunetta, Jesse Mez, Richard Mayeux, Jonathan L Haines, Margaret A Pericak-Vance, Gerard Schellenberg, Gyungah R Jun, Lindsay A Farrer
BACKGROUND: Simultaneous consideration of two neuropathological traits related to Alzheimer's disease (AD) has not been attempted in a genome-wide association study. METHODS: We conducted genome-wide pleiotropy analyses using association summary statistics from the Beecham et al. study (PLoS Genet 10:e1004606, 2014) for AD-related neuropathological traits, including neuritic plaque (NP), neurofibrillary tangle (NFT), and cerebral amyloid angiopathy (CAA). Significant findings were further examined by expression quantitative trait locus and differentially expressed gene analyses in AD vs...
February 20, 2018: Alzheimer's Research & Therapy
Ryuichi Nishii, Tatsuya Higashi, Shinya Kagawa, Chio Okuyama, Yoshihiko Kishibe, Masaaki Takahashi, Tomoko Okina, Norio Suzuki, Hiroshi Hasegawa, Yasuhiro Nagahama, Koichi Ishizu, Naoya Oishi, Hiroyuki Kimura, Hiroyuki Watanabe, Masahiro Ono, Hideo Saji, Hiroshi Yamauchi
OBJECTIVE: Recently, a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2-18 F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)- N-methylpyridin-2-amine (18 F-FPYBF-2) has been validated as a tracer for amyloid imaging and it was found that18 F-FPYBF-2 PET/CT is a useful and reliable diagnostic tool for the evaluation of AD (Higashi et al. Ann Nucl Med, , 2018). The aim of this study was to assess the biodistribution and radiation dosimetry of diagnostic dosages of18 F-FPYBF-2 in normal healthy volunteers as a first-in-man study...
February 16, 2018: Annals of Nuclear Medicine
Ulla Vogel, Flemming R Cassee
Epidemiological studies link inhalation of particles to increased risk of cardiovascular disease. Inhaled particles may induce cardiovascular disease by several different mechanisms including translocation of particles to systemic circulation, activation of airway sensory nerves resulting in autonomic imbalance and particle-induced pulmonary inflammation and acute phase response.The acute phase response is the systemic response to acute and chronic inflammatory states caused by for example bacterial infection, virus infection, trauma and infarction...
February 12, 2018: Particle and Fibre Toxicology
L Li, X J Duan, Y Sun, Y Lu, H Y Xu, Q Z Wang, H Y Wang
Objective: To evaluate the sensitivity and specificity of immunohistochemistry (IHC) in the classification of cardiac amyloidosis on endomyocardial biopsy (EMB) and heart allograft. Methods: Twenty cardiac tissues from 19 patients at Fuwai Hospital from January, 1990 to April, 2017 with histopathologic features of amyloidosis and Congo red staining positivity were included. IHC was performed with monoclonal antibodies against AA amyloid and polyclonal antibodies against transthyretin (ATTR), λ-light chain (AL-λ), κ-light chain (AL-κ), ApoAⅠ, ApoAⅡ, ApoA Ⅳ and β(2)-microglobin...
February 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Pooja Phull, Vaishali Sanchorawala, Lawreen H Connors, Gheorghe Doros, Frederick L Ruberg, John L Berk, Shayna Sarosiek
OBJECTIVE: To identify the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with transthyretin (ATTR) amyloidosis. PATIENTS AND METHODS: We performed a retrospective analysis of patients with biopsy-proven ATTRwt (wild-type transthyretin amyloid protein) and genopositive ATTR V122I (valine-to-isoleucine substitution at position 122 of the TTR gene) amyloidosis evaluated at the Amyloidosis Center at Boston University and Boston Medical Center between 1 January 2003 and 31 December 2016...
February 9, 2018: Amyloid: the International Journal of Experimental and Clinical Investigation
Matthew J Flick, Joseph S Palumbo
Platelets were first implicated in the pathogenesis of cancer and inflammatory pathologies decades ago, but an understanding of the mechanisms coupling platelet function to cancer progression is still a work in progress. In their paper, Servais et al. push the field forward by illustrating that platelets represent a crucial link between inflammatory disease and tumorigenesis [1]. This interesting paper presents data showing that platelets promote intestinal tumorigenesis in the context of inflammatory colitis by supporting the recruitment and/or expansion of myeloid-derived suppressor cells (MDSCs)...
February 8, 2018: Journal of Thrombosis and Haemostasis: JTH
Alexei V Finkelstein, Nikita V Dovidchenko, Oxana Valerianovna Galzitskaya
An abnormal dependence of the rate of amyloid formation on protein concentration has been recently observed by Meisl et al. for Aβ40 peptides associated with Alzheimer's disease. To explain this effect, Meisl et al. proposed a novel mechanism of fibril growth: the fibril-catalyzed initiation of fibril formation. In this paper we offer an alternative explanation of the observed anomalous kinetics: formation of metastable oligomers competing with fibril formation by decreasing the concentration of the fibril-forming free monomers...
February 7, 2018: Journal of Physical Chemistry Letters
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