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Amyloid in blood

Annamaria Cattaneo, Nadia Cattane, Samantha Galluzzi, Stefania Provasi, Nicola Lopizzo, Cristina Festari, Clarissa Ferrari, Ugo Paolo Guerra, Barbara Paghera, Cristina Muscio, Angelo Bianchetti, Giorgio Dalla Volta, Marinella Turla, Maria Sofia Cotelli, Michele Gennuso, Alessandro Prelle, Orazio Zanetti, Giulia Lussignoli, Dario Mirabile, Daniele Bellandi, Simona Gentile, Gloria Belotti, Daniele Villani, Taoufiq Harach, Tristan Bolmont, Alessandro Padovani, Marina Boccardi, Giovanni B Frisoni
The pathway leading from amyloid-β deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients...
August 31, 2016: Neurobiology of Aging
Maria Gregori, Mark Taylor, Elisa Salvati, Francesca Re, Simona Mancini, Claudia Balducci, Gianluigi Forloni, Vanessa Zambelli, Silvia Sesana, Maria Michael, Christos Michail, Claire Tinker-Mill, Oleg Kolosov, Michael Scherer, Stephen Harris, Nigel J Fullwood, Massimo Masserini, David Allsop
Aggregation of Amyloid-β peptide (Aβ) is a key event in the pathogenesis of Alzheimer's disease (AD). We investigated the effects of nanoliposomes decorated with the retro-inverso peptide RI-OR2-TAT (Ac-rGffvlkGrrrrqrrkkrGy-NH2) on the aggregation and toxicity of Aβ. Remarkably low concentrations of these peptide inhibitor nanoparticles (PINPs) were required to inhibit the formation of Aβ oligomers and fibrils in vitro, with 50% inhibition occurring at a molar ratio of ~1:2000 of liposome-bound RI-OR2-TAT to Aβ...
October 18, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Hossein Derakhshankhah, Mohammad Javad Hajipour, Ebrahim Barzegari, Alireza Lotfabadi, Maryam Ferdousi, Ali Akbar Saboury, Eng-Poh Ng, Mohammad Raoufi, Hussein Awala, Svetlana Mintova, Rassoul Dinarvand, Morteza Mahmoudi
EMT-type zeolite nanoparticles (EMT NPs) with diameter smaller than 12 nm and uniform pore size of 7.3 Å have shown high selective affinity toward plasma protein (fibrinogen). Besides, the EMT NPs have demonstrated no adverse effect on blood coagulation hemostasis. Therefore, it was envisioned that the EMT NPs could inhibit possible β-Amyloid (Aβ)-fibrinogen interactions that result in the formation of structurally abnormal clots, which are resistant to lysis, in cerebral vessels of patients with Alzheimer disease (AD)...
October 21, 2016: ACS Applied Materials & Interfaces
K Rygiel
Alzheimer's disease (AD) is a neurodegenerative disease, in which an accumulation of toxic amyloid beta in the brain precedes the emergence of clinical symptoms. AD spectrum consists of presymptomatic, early symptomatic, and symptomatic phase of dementia. At present, no pharmacotherapy exists to modify or reverse a course of AD, and only symptomatic treatments are available. Many elderly patients, diagnosed with multiple medical conditions (such as cardiovascular diseases, Type 2 diabetes mellitus, and cerebrovascular diseases) are at increased risk of the development of mild cognitive impairment (MCI), AD, and vascular dementia...
October 2016: Journal of Postgraduate Medicine
Chih-Hsiang Hsu, Sheue-Er Wang, Ching-Lung Lin, Chun-Jen Hsiao, Shuenn-Jyi Sheu, Chung-Hsin Wu
In this study, we have reported the herbal formula B401 that has neuroprotective effects via multifunction, multitarget characteristics. It is possible that the herbal formula B401 may also provide new insights for AD. Here, we studied protective effects in the Tet-On Aβ42-GFP SH-SY5Y cell model and the APP/PS1/Tau triple transgenic mouse model by the herbal formula B401. In in vitro experiments, we showed that the herbal formula B401 treatment effectively reduces glutamate-induced excitotoxicity and acetylcholinesterase activity in Tet-On Aβ42-GFP SH-SY5Y cells...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Lara Ordóñez-Gutiérrez, Adrián Posado-Fernández, Davoud Ahmadvand, Barbara Lettiero, Linping Wu, Marta Antón, Orfeu Flores, Seyed Moein Moghimi, Francisco Wandosell
The accumulation of extracellular amyloid-beta (Aβ) and intracellular neurofibrillary tangles (hyper-phosphorylated Tau) in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). Active and passive immunotherapy may limit cerebral Aβ deposition and/or accelerate its clearance. With the aid of a newly characterized monoclonal anti-Aβ antibody we constructed immunoPEGliposomes with high avidity for capturing Aβ in the periphery. The functionality of these vesicles in modulating Aβ uptake by both human brain capillary endothelial hCMEC/D3 cells (suppressing uptake) and THP-1 phagocytes (stimulating uptake) was confirmed in vitro...
August 2, 2016: Biomaterials
Akihiko Hosoi, Yu Su, Masaharu Torikai, Hirofumi Jono, Daisuke Ishikawa, Kenji Soejima, Hirofumi Higuchi, Jianying Guo, Mitsuharu Ueda, Genki Suenaga, Hiroaki Motokawa, Tokunori Ikeda, Satoru Senju, Toshihiro Nakashima, Yukio Ando
Familial amyloidotic polyneuropathy (FAP) is a systemic amyloidosis mainly caused by amyloidogenic transthyretin (ATTR). This incurable disease causes death approximately 10 years after onset. Although it has been widely accepted that conformational change of the monomeric form of transthyretin (TTR) is very important for amyloid formation and deposition in the organs, no effective therapy targeting this step is available. In this study, we generated a mouse monoclonal antibody T24 which recognized the cryptic epitope of conformationally-changed TTR...
October 7, 2016: Journal of Biological Chemistry
Eric D Hamlett, Edward J Goetzl, Aurélie Ledreux, Vitaly Vasilevko, Heather A Boger, Angela LaRosa, David Clark, Steven L Carroll, Maria Carmona Iragui, Juan Fortea, Elliott J Mufson, Marwan Sabbagh, Abdul H Mohammed, Dean Hartley, Eric Doran, Ira T Lott, Ann-Charlotte Granholm
INTRODUCTION: Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non-AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid-β (Aβ) peptides and phosphorylated-tau in neuronal exosomes may document preclinical AD. METHODS: AD neuropathogenic proteins Aβ1-42, P-T181-tau, and P-S396-tau were quantified by enzyme-linked immunosorbent assays in extracts of neuronal exosomes purified from blood of individuals with DS and age-matched controls...
October 15, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Sven Haller, Greg Zaharchuk, David L Thomas, Karl-Olof Lovblad, Frederik Barkhof, Xavier Golay
Arterial spin labeling (ASL) is a magnetic resonance (MR) imaging technique used to assess cerebral blood flow noninvasively by magnetically labeling inflowing blood. In this article, the main labeling techniques, notably pulsed and pseudocontinuous ASL, as well as emerging clinical applications will be reviewed. In dementia, the pattern of hypoperfusion on ASL images closely matches the established patterns of hypometabolism on fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) images due to the close coupling of perfusion and metabolism in the brain...
November 2016: Radiology
Zhanna Kobalava
The burden of cardiovascular diseases (CVD) in general and heart failure (HF) in particular continues to increase worldwide. CVD are major contributors to death and morbidity and recognized as important drivers of healthcare expenditure. Chronic overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in human hypertension and HF pathophysiology. RAAS is fundamental in the overall regulation of cardiovascular homeostasis through the actions of hormones, which regulate vascular tone, and specifically blood pressure through vasoconstriction and renal sodium and water retention...
September 2016: Journal of Hypertension
Shokei Kim-Mitsuyama
There is accumulating evidence that RAS inhibitors not only reduce blood pressure, but also exert pleiotropic effects, including a renoprotective effect, amelioration of insulin resistance, reduction in onset of diabetes, and suppression of cardiovascular remodelling,. However, the definite benefit of RAS inhibition in treatment of hypertension with CKD or DM is not conclusive. We previously performed the OlmeSartan and Calcium Antagonists Randomized (OSCAR) study comparing the preventive effect of high-dose ARB therapy versus ARB plus CCB combination therapy on cardiovascular morbidity and mortality in 1164 Japanese elderly hypertensive patients with baseline type 2 diabetes and/or CVD (Am J Med (2012))...
September 2016: Journal of Hypertension
Sverre Kjeldsen
There is a whole armament of good drugs for treatment of hypertension including diuretics, calcium antagonist, angiotensin receptor antagonists and angiotensin converting enzyme inhibitors. Secondary drugs mostly used for special indications include beta-blockers, alpha-blockers, mineralocorticoid receptor antagonists (aldosterone antagonists), renin-inhibitors, centrally acting drugs, direct vasodilators and others.A variety of new drugs targeting different pressor mechanism exist and have partly been studies experimentally but will unlikely make it to clinical use in human hypertension...
September 2016: Journal of Hypertension
Koki Takane, Yu Hasegawa, Lin Bowen, Takashi Yokoo, Shokei Kim-Mitsuyama
OBJECTIVE: Increasing evidences suggest that patients with Alzheimer's disease (AD) show not only cognitive impairment but also physical disorder including cardiac dysfunction and sarcopenia. In this study, we investigated whether central angiotensin II, inducer of oxidative stress, led to the organ dysfunction in a mouse model of AD. DESIGN AND METHOD: 5XFAD which is an animal model of AD and C57BL/6 (WT) were each assigned to 1) normal saline and 2) angiotensin II (20 mg/kg/h) groups...
September 2016: Journal of Hypertension
Elizabeth M S Schmidt, Mads Kjelgaard-Hansen, Funmilola Thomas, Asta Tvarijonaviciute, José J Cerón, P David Eckersall
BACKGROUND: Dioctophyme renale is a nematode parasite of dogs, usually found in the right kidney, causing severe damage to the renal parenchyma. OBJECTIVES: The objective was to evaluate the acute phase response in dogs naturally infected with this Giant Kidney Worm and the possible effects of nephrectomy on circulating concentrations of select acute phase proteins (APP) such as serum amyloid A (SAA), C-reactive protein (CRP), and haptoglobin (HP). METHODS: Nephrectomy was performed in infected dogs and the worms were collected for identification...
October 17, 2016: Veterinary Clinical Pathology
Ashvini Keshavan, Amanda Heslegrave, Henrik Zetterberg, Jonathan M Schott
Biomarkers in Alzheimer's disease (AD) have the potential to allow early and more accurate diagnosis, predict disease progression, stratify individuals and track response to candidate therapies in drug trials. The first fluid biomarkers reflecting aspects of AD neuropathology were identified in cerebrospinal fluid (CSF) in the 1990s. Three CSF biomarkers (amyloid-β 1-42, total tau and phospho-tau) have consistently been shown to have diagnostic utility and are incorporated into the new diagnostic criteria for AD...
October 13, 2016: Molecular Diagnosis & Therapy
Scott E Counts, Milos D Ikonomovic, Natosha Mercado, Irving E Vega, Elliott J Mufson
The recent failures of potential disease-modifying drugs for Alzheimer's disease (AD) may reflect the fact that the enrolled participants in clinical trials are already too advanced to derive a clinical benefit. Thus, well-validated biomarkers for the early detection and accurate diagnosis of the preclinical stages of AD will be crucial for therapeutic advancement. The combinatorial use of biomarkers derived from biological fluids, such as cerebrospinal fluid (CSF), with advanced molecular imaging and neuropsychological testing may eventually achieve the diagnostic sensitivity and specificity necessary to identify people in the earliest stages of the disease when drug modification is most likely possible...
October 13, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
E Candeias, A I Duarte, I Sebastião, M A Fernandes, A I Plácido, C Carvalho, S Correia, R X Santos, R Seiça, M S Santos, C R Oliveira, P I Moreira
Type 2 diabetes (T2D) is a highly concerning public health problem of the twenty-first century. Currently, it is estimated that T2D affects 422 million people worldwide with a rapidly increasing prevalence. During the past two decades, T2D has been widely shown to have a major impact in the brain. This, together with the cognitive decline and increased risk for dementia upon T2D, may arise from the complex interaction between normal brain aging and central insulin signaling dysfunction. Among the several features shared between T2D and some neurodegenerative disorders (e...
October 11, 2016: Molecular Neurobiology
Farron L McIntee, Patrizia Giannoni, Steven Blais, George Sommer, Thomas A Neubert, Agueda Rostagno, Jorge Ghiso
Amyloid β (Aβ) is the major constituent of the brain deposits found in parenchymal plaques and cerebral blood vessels of patients with Alzheimer's disease (AD). Several lines of investigation support the notion that synaptic pathology, one of the strongest correlates to cognitive impairment, is related to the progressive accumulation of neurotoxic Aβ oligomers. Since the process of oligomerization/fibrillization is concentration-dependent, it is highly reliant on the homeostatic mechanisms that regulate the steady state levels of Aβ influencing the delicate balance between rate of synthesis, dynamics of aggregation, and clearance kinetics...
2016: Frontiers in Aging Neuroscience
Aruna K Mora, Sushant Murudkar, A Alamelu, Prabhat K Singh, Subrata Chattopadhyay, Sukhendu Nath
Early detection of amyloid fibrils is very important for the timely diagnosis of several neurological diseases. Thioflavin-T (ThT) is a gold standard fluorescent probe for amyloid fibrils and has been used for the last few decades. However, due to its positive charge, ThT is incapable of crossing the blood-brain barrier and cannot be used for in vivo imaging of fibrils. In the present work, we synthesized a neutral ThT derivative, 2-[2'-Me,4'-(dimethylamino)phenyl]benzothiazole (2Me-DABT), which showed a strong affinity towards the amyloid fibrils...
October 11, 2016: Chemistry: a European Journal
Elisanne Alm Biemans, Lieke Jäkel, Robert Mw de Waal, H Bea Kuiperij, Marcel M Verbeek
Alzheimer's disease and cerebral amyloid angiopathy are characterized by accumulation of amyloid-β (Aβ) at the cerebrovasculature due to decreased clearance at the blood-brain barrier (BBB). However, the exact mechanism of Aβ clearance across this barrier has not been fully elucidated. The hCMEC/D3 cell line has been characterized as a valid model for the BBB. In this study we evaluated the use of this model to study Aβ clearance across the BBB, with an emphasis on brain-to-blood directional permeability...
October 11, 2016: Journal of Neuroscience Research
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