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Amyloid in blood

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https://www.readbyqxmd.com/read/28719802/cerebral-hypoperfusion-is-not-associated-with-an-increase-in-%C3%AE-amyloid-pathology-in-middle-aged-or-elderly-people
#1
O Hansson, S Palmqvist, H Ljung, T Cronberg, D van Westen, R Smith
INTRODUCTION: It is hypothesized that cerebral hypoperfusion promotes the development of Alzheimer pathology. We therefore studied whether longstanding cerebral hypoperfusion is associated with Alzheimer pathology in nondemented humans. METHODS: Cerebral blood flow and β-amyloid ((18)F-Flutemetamol) positron emission tomography retention were assessed in eleven patients with unilateral occlusion of precerebral arteries resulting in chronic and uneven hypoperfusion...
July 15, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28719622/characterization-of-plasma-metal-profiles-in-alzheimer-s-disease-using-multivariate-statistical-analysis
#2
Chunmei Guan, Rui Dang, Yu Cui, Liyan Liu, Xiaobei Chen, Xiaoyu Wang, Jingli Zhu, Donggang Li, Junwei Li, Decai Wang
The exact cause of Alzheimer's disease (AD) and the role of metals in its etiology remain unclear. We have used an analytical approach, based on inductively coupled plasma mass spectrometry coupled with multivariate statistical analysis, to study the profiles of a wide range of metals in AD patients and healthy controls. AD cannot be cured and the lack of sensitive biomarkers that can be used in the early stages of the disease may contribute to this treatment failure. In the present study, we measured plasma levels of amyloid-β1-42(0...
2017: PloS One
https://www.readbyqxmd.com/read/28715596/influence-of-physical-exercise-on-%C3%AE-amyloid-%C3%AE-synuclein-and-tau-accumulation-an-in-vitro-model-of-oxidative-stress-in-human-red-blood-cells
#3
C Iofrida, S Daniele, D Pietrobono, J Fusi, F Galetta, M L Trincavelli, U Bonuccelli, F Franzoni, C Martini
A common pathological feature of neurodegenerative disorders (NDs), such as Alzheimer's (AD) and Parkinson's (PD) diseases, is the abnormal accumulation and misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1-42 (Aβ) and tau, in brain and in peripheral tissues too. Oxidative stress has been proved to be involved in NDs at various levels and, in particular, in such protein alterations, on the contrary physical activity is emerging as a counteracting factor in NDs. In the present work, the content of Aβ, α-syn and tau in red blood cells (RBCs) derived from ten endurance athletes (ATHL) and ten sedentary volunteers (SED) were compared before and after in vitrooxidative stress treatment...
July 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/28713245/multifaceted-roles-of-metzincins-in-cns-physiology-and-pathology-from-synaptic-plasticity-and-cognition-to-neurodegenerative-disorders
#4
REVIEW
Patrycja Brzdak, Daria Nowak, Grzegorz Wiera, Jerzy W Mozrzymas
The extracellular matrix (ECM) and membrane proteolysis play a key role in structural and functional synaptic plasticity associated with development and learning. A growing body of evidence underscores the multifaceted role of members of the metzincin superfamily, including metalloproteinases (MMPs), A Disintegrin and Metalloproteinases (ADAMs), A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs) and astacins in physiological and pathological processes in the central nervous system (CNS)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28711713/surprisingly-high-stability-of-the-a%C3%AE-oligomer-eliminating-all-d-enantiomeric-peptide-d3-in-media-simulating-the-route-of-orally-administered-drugs
#5
Anne Elfgen, Beatrix Santiago-Schübel, Lothar Gremer, Janine Kutzsche, Dieter Willbold
The aggregation of the amyloid β protein (Aβ) plays an important role in the pathology of Alzheimer's disease. Previously, we have developed the all-d-enantiomeric peptide D3, which is able to eliminate neurotoxic Aβ oligomers in vitro and improve cognition in a transgenic Alzheimer's disease mouse model in vivo even after oral administration. d-Peptides are expected to be more resistant against enzymatic proteolysis compared to their l-enantiomeric equivalents, and indeed, a pharmacokinetic study with tritiated D3 revealed the oral bioavailability to be about 58%...
July 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28710249/amyloid-precursor-protein-in-pancreatic-islets
#6
Joshua Kulas, Kendra Puig, Colin K Combs
The amyloid precursor protein (APP) has been extensively investigated for its role in the production of amyloid beta (Aβ), a plaque forming peptide in Alzheimer's disease (AD). Epidemiological evidence suggests type 2 diabetes is a risk factor for AD. The pancreas is an essential regulator of blood glucose levels through the secretion of the hormones insulin and glucagon. Pancreatic dysfunction is a well characterized consequence of type 1 and type 2 diabetes. In this study we have examined the expression and processing of pancreatic APP to test the hypothesis that APP may play a role in pancreatic function and the pathophysiology of diabetes...
July 14, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28702365/abnormal-amyloid-%C3%AE-42-expression-and-increased-oxidative-stress-in-plasma-of-ckd-patients-with-cognitive-dysfunction-a-small-scale-case-control-study-comparison-with-alzheimer-s-disease
#7
G Vinothkumar, C Kedharnath, S Krishnakumar, S Sreedhar, K Preethikrishnan, S Dinesh, A Sundaram, D Balakrishnan, G Shivashekar, Sureshkumar, P Venkataraman
BACKGROUND: Cognitive dysfunction has been increasingly recognized in chronic kidney disease (CKD) patients. Senile plaques are important pathophysiological characteristic of cognitive dysfunction. The major component of plaques is the amyloid β (Aβ) peptide released from proteolytic cleavage of amyloid precursor protein (APP). Plasma Aβ has been a focus of the growing literature on blood based biomarkers for cognitive dysfunction. Oxidative stress is prevalent in CKD and it plays an important role in cognitive dysfunction...
December 2017: BBA Clinical
https://www.readbyqxmd.com/read/28701379/loss-of-clusterin-shifts-amyloid-deposition-to-the-cerebrovasculature-via-disruption-of-perivascular-drainage-pathways
#8
Aleksandra M Wojtas, Silvia S Kang, Benjamin M Olley, Maureen Gatherer, Mitsuru Shinohara, Patricia A Lozano, Chia-Chen Liu, Aishe Kurti, Kelsey E Baker, Dennis W Dickson, Mei Yue, Leonard Petrucelli, Guojun Bu, Roxana O Carare, John D Fryer
Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) peptide deposition in brain parenchyma as plaques and in cerebral blood vessels as cerebral amyloid angiopathy (CAA). CAA deposition leads to several clinical complications, including intracerebral hemorrhage. The underlying molecular mechanisms that regulate plaque and CAA deposition in the vast majority of sporadic AD patients remain unclear. The clusterin (CLU) gene is genetically associated with AD and CLU has been shown to alter aggregation, toxicity, and blood-brain barrier transport of Aβ, suggesting it might play a key role in regulating the balance between Aβ deposition and clearance in both brain and blood vessels...
July 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28700245/synthesis-and-evaluation-of-diphenyl-conjugated-imidazole-derivatives-as-potential-glutaminyl-cyclase-inhibitors-for-treatment-of-alzheimer-s-disease
#9
Manman Li, Yao Dong, Xi Yu, Yue Li, Yongdong Zou, Yizhi Zheng, Zhendan He, Zhigang Liu, Jun-Min Quan, Xianzhang Bu, Haiqiang Wu
High expression of glutaminyl cyclase (QC) contributes to the initiation of Alzheimer's disease (AD) by catalyzing the generation of neurotoxic pyroglutamate (pE)-modified β-amyloid (Aβ) peptides. Preventing the generation of pE-Aβs by QC inhibition has been suggested as a novel approach to a disease-modifying therapy for AD. In this work, a series of diphenyl conjugated imidazole derivatives (DPCIs) was rationally designed and synthesized. Analogues with this scaffold exhibited potent inhibitory activity against human QC (hQC), and good in vitro blood brain barrier (BBB) permeability...
July 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28699522/targeting-human-astrocytes-calcium-sensing-receptors-for-treatment-of-alzheimer-s-disease
#10
Anna Chiarini, Ubaldo Armato, James F Whitfield, Ilaria Dal Pra
Understanding the pathophysiology of Alzheimer's disease (AD) in the principal human neural cells is necessary for finding therapeutics for this illness. To help do this, we have been using freshly cultured functionally normal cerebral cortical adult human astrocytes (NAHAs) and postnatal neurons. The findings show that amyloid-β oligomers (Aβ-os) binding to calcium-sensing receptors (CaSRs) on NAHAs and neuron surfaces trigger signals capable of driving AD pathogenesis. This Aβ•CaSR signalling shifts the amyloid precursor protein (APP) from its α-secretase shedding producing neurotrophic/neuroprotective soluble (s)APPα to its β-secretase cleaving engendering AD-driving Aβ42/Aβ42-os peptides...
July 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28697660/neuroprotective-effects-of-a-biodegradable-poly-lactic-co-glycolic-acid-ginsenoside-rg3-nanoformulation-a-potential-nanotherapy-for-alzheimer-s-disease
#11
Ravikumar Aalinkeel, Hilliard L Kutscher, Ajay Singh, Katherine Cwiklinski, Noor Khechen, Stanley A Schwartz, Paras N Prasad, Supriya D Mahajan
It is well established that overproduction and accumulation of the β-amyloid (Aβ) peptide 1-42 (Aβ(1-42)) is a trigger of the pathological cascade in Alzheimer's disease (AD) that manifests as cognitive impairment. Ginsenoside Rg3 is an important constituent of ginseng, plays an essential role in memory and improved cognition, and is known to produce antioxidant effects via the reduction of free radicals. Therefore, ginsenoside Rg3 may be a promising candidate as a neuroprotective agent for the treatment of AD...
July 12, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28697558/comparative-analysis-of-cortical-microinfarcts-and-microbleeds-using-3-0-tesla-postmortem-magnetic-resonance-images-and-histopathology
#12
Atsushi Niwa, Yuichiro Ii, Akihiro Shindo, Ko Matsuo, Hidehiro Ishikawa, Akira Taniguchi, Shinichi Takase, Masayuki Maeda, Hajime Sakuma, Hiroyasu Akatsu, Yoshio Hashizume, Hidekazu Tomimoto
Microvascular lesions including cortical microinfarctions (CMIs) and cerebral lobar microbleeds (CMBs) are usually caused by cerebral amyloid angiopathy (CAA) in the elderly and are correlated with cognitive decline. However, their radiological-histopathological coincidence has not been revealed systematically with widely used 3-Tesla (3T) magnetic resonance imaging (MRI). The purpose of the present study is to delineate the histopathological background corresponding to MR images of these lesions. We examined formalin-fixed 10-mm thick coronal brain blocks from 10 CAA patients (five were also diagnosed with Alzheimer's disease, three with dementia with Lewy bodies, and two with CAA only) with dementia and six non CAA patients with neurodegenerative disease...
July 5, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28696436/reduced-trpc6-mrna-levels-in-the-blood-cells-of-patients-with-alzheimer-s-disease-and-mild-cognitive-impairment
#13
R Lu, J Wang, R Tao, J Wang, T Zhu, W Guo, Y Sun, H Li, Y Gao, W Zhang, C J Fowler, Q Li, S Chen, Z Wu, C L Masters, C Zhong, N Jing, Y Wang, Y Wang
Transient receptor potential canonical 6 (TRPC6) inhibits β-amyloid (Aβ) production. Hyperforin, the TRPC6 agonist, reduces Aβ levels and improves cognitive performance in Alzheimer's disease (AD) models. However, it's unknown whether TRPC6 expression is changed in AD patients. In this case-control study, we measured TRPC6 expression levels in the peripheral blood cells of four independent AD sets from five hospitals and one mild cognitive impairment (MCI) set from a local community (229 AD, 70 MCI, 40 Parkinson disease and 359 controls from China, total n=698) using quantitative real-time PCR assay...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28696433/elevated-plasma-ferritin-in-elderly-individuals-with-high-neocortical-amyloid-%C3%AE-load
#14
K Goozee, P Chatterjee, I James, K Shen, H R Sohrabi, P R Asih, P Dave, C ManYan, K Taddei, S J Ayton, M L Garg, J B Kwok, A I Bush, R Chung, J S Magnussen, R N Martins
Ferritin, an iron storage and regulation protein, has been associated with Alzheimer's disease (AD); however, it has not been investigated in preclinical AD, detected by neocortical amyloid-β load (NAL), before cognitive impairment. Cross-sectional analyses were carried out for plasma and serum ferritin in participants in the Kerr Anglican Retirement Village Initiative in Aging Health cohort. Subjects were aged 65-90 years and were categorized into high and low NAL groups via positron emission tomography using a standard uptake value ratio cutoff=1...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28692534/blood-neuron-derived-exosomes-as-biomarkers-of-cognitive-impairment-in-hiv
#15
Bing Sun, Pranjali Dalvi, Linda Abadjian, Norina Tang, Lynn Pulliam
OBJECTIVE: To investigate proteins associated with neuronal damage in plasma neuron-derived exosomes (NDE) of HIV-infected subjects as a liquid biomarker for cognitive impairment. METHODS: Plasma NDE were isolated using precipitation and immunoadsorption with antibody to a cell surface specific neuronal marker. Total exosomes and NDE were enumerated, characterized and proteins extracted and targets quantified by ELISA. RESULTS: Plasma NDE from 23 HIV seropositive individuals of which 11 had mild cognitive impairment, and 12 HIV seronegative controls of which 3 had cognitive impairment were isolated...
July 7, 2017: AIDS
https://www.readbyqxmd.com/read/28692002/impact-of-work-task-related-acute-occupational-smoke-exposures-on-select-proinflammatory-immune-parameters-in-wildland-firefighters
#16
Anna M Adetona, Olorunfemi Adetona, Robert M Gogal, David Diaz-Sanchez, Stephen L Rathbun, Luke P Naeher
OBJECTIVE: A repeated measures study was used to assess the effect of work tasks on select proinflammatory biomarkers in firefighters working at prescribed burns. METHODS: Ten firefighters and two volunteers were monitored for particulate matter and carbon monoxide on workdays, January to July 2015. Before and after workshift dried blood spots were analyzed for inflammatory mediators using the Meso Scale Discovery assay, while blood smears were used to assess leukocyte parameters...
July 2017: Journal of Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/28680349/serum-level-of-hmgb1-protein-and-inflammatory-markers-in-patients-with-secondary-peritonitis-time-course-and-the-association-with-clinical-status
#17
Ljiljana Milić, Ilijana Grigorov, Slobodan Krstić, Miljan S Ćeranić, Bojan Jovanović, Jelena Stevanović, Predrag Peško
BACKGROUND: Intra-abdominal infection in secondary peritonitis drives as excessive production of inflammatory mediators and the development of systemic inflammatory response syndrome (SIRS) or sepsis. Finding a specific marker to distinguish SIRS from sepsis would be of immense clinical importance for the therapeutic approach. It is assumed that high-mobility group box 1 protein (HMGB1) could be such a marker. In this study, we examined the time course changes in the blood levels of HMGB1, C-reactive protein (CRP), procalcitonin (PCT) and serum amyloid A (SAA) in patients with secondary peritonitis who developed SIRS or sepsis...
January 2017: Journal of Medical Biochemistry
https://www.readbyqxmd.com/read/28677373/commitment-of-protein-p53-and-amyloid-beta-peptide-a%C3%AE-in-aging-of-human-cerebellum
#18
Danuta Maślińska, Milena Laure-Kamionowska, Dariusz Szukiewicz, Sławomir Maśliński, Krystyna Księżopolska-Orłowska
Protein p53 is known to induce the cell cycle arrest and apoptosis in response to a variety of cellular distress signals and DNA damage. A recent study has demonstrated that in blood cells of aging subjects, p53 may induce early pathological changes that precede the amyloidogenic cascade. However, it is not clear whether p53 participates in the local deposition of amyloid-beta peptide (Aβ) in the nerve tissue of normal aging subjects. Therefore, in the present study, we analyse the distribution of both (Aβ and p53) proteins in the cerebellum of individuals without any history of dementia or other neurological illness who died suddenly in traffic accidents...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28674847/a-new-integrated-dual-time-point-amyloid-pet-mri-data-analysis-method
#19
Diego Cecchin, Henryk Barthel, Davide Poggiali, Annachiara Cagnin, Solveig Tiepolt, Pietro Zucchetta, Paolo Turco, Paolo Gallo, Anna Chiara Frigo, Osama Sabri, Franco Bui
PURPOSE: In the initial evaluation of patients with suspected dementia and Alzheimer's disease, there is no consensus on how to perform semiquantification of amyloid in such a way that it: (1) facilitates visual qualitative interpretation, (2) takes the kinetic behaviour of the tracer into consideration particularly with regard to at least partially correcting for blood flow dependence, (3) analyses the amyloid load based on accurate parcellation of cortical and subcortical areas, (4) includes partial volume effect correction (PVEC), (5) includes MRI-derived topographical indexes, (6) enables application to PET/MRI images and PET/CT images with separately acquired MR images, and (7) allows automation...
July 4, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28673587/bariatric-surgery-may-reduce-the-risk-of-alzheimer-s-diseases-through-glp-1-mediated-neuroprotective-effects
#20
Hari B Keshava, Ashkan Mowla, Leslie J Heinberg, Philip R Schauer, Stacy A Brethauer, Ali Aminian
Obesity and diabetes are associated with deficits in multiple neurocognitive domains and increased risk for dementia. Over the last two decades, there has been a significant increase in bariatric and metabolic surgery worldwide, driven by rising intertwined pandemics of obesity and diabetes, along with improvement in surgical techniques. Patients undergoing bariatric surgery achieve a significant decrease in their excess weight and a multitude of sequela associated with obesity, diabetes, and metabolic syndrome...
July 2017: Medical Hypotheses
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