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Amyloid in blood

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https://www.readbyqxmd.com/read/28334103/neuronal-and-peripheral-pentraxins-modify-glutamate-release-and-may-interact-in-blood-brain-barrier-failure
#1
Damian M Cummings, Tiffanie A Benway, Hinze Ho, Angelo Tedoldi, Monica M Fernandes Freitas, Lion Shahab, Christina E Murray, Angela Richard-Loendt, Sebastian Brandner, Tammaryn Lashley, Dervis A Salih, Frances A Edwards
Neuronal pentraxin 1 (NPTX1) has been implicated in Alzheimer's disease, being present in and around dystrophic neurons in plaques, affecting glutamatergic transmission postsynaptically and mediating effects of amyloidβ. Here, we confirm the presence of NPTX1 around plaques in postmortem Alzheimer's disease brain and report that acutely applied human NPTX1 increases paired-pulse ratio at mouse CA3-CA1 hippocampal synapses, indicating a decrease in glutamate release. In contrast, chronic exposure to NPTX1, NPTX2, or NPTX receptor decreases paired-pulse ratio, mimicking some of the earliest changes in mice expressing familial Alzheimer's disease genes...
February 23, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28330509/chemically-treated-plasma-a%C3%AE-is-a-potential-blood-based-biomarker-for-screening-cerebral-amyloid-deposition
#2
Jong-Chan Park, Sun-Ho Han, Hyun Jin Cho, Min Soo Byun, Dahyun Yi, Young Min Choe, Seokjo Kang, Eun Sun Jung, Su Jin Won, Eun Hye Kim, Yu Kyeong Kim, Dong Young Lee, Inhee Mook-Jung
BACKGROUND: Plasma β-amyloid (Aβ) is a potential candidate for an Alzheimer's disease (AD) biomarker because blood is an easily accessible bio-fluid, which can be collected routinely, and Aβ is one of the major hallmarks of AD pathogenesis in the brain. However, the association between plasma Aβ levels and AD diagnosis is still unclear due to the instability and inaccurate measurements of plasma Aβ levels in the blood of patients with AD. If a consistent value of plasma Aβ from the blood can be obtained, this might help determine whether plasma Aβ is a potential biomarker for AD diagnosis...
March 22, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28326436/reference-region-selection-and-the-association-between-the-rate-of-amyloid-accumulation-over-time-and-the-baseline-amyloid-burden
#3
Janusch Blautzik, Matthias Brendel, Julia Sauerbeck, Sebastian Kotz, Franziska Scheiwein, Peter Bartenstein, John Seibyl, Axel Rominger
Relative quantitative analysis of amyloid plaque burden in Alzheimer's disease (AD) patients can be reported as standardized uptake value ratio (SUVR) from positron emission tomography (PET). Here, the SUVR is the ratio of the mean amyloid radioligand retention in a composite (COMP) neocortical volume of interest (VOI) to that in a reference VOI, such as the cerebellum, brainstem (BST)/pons, or white matter (WM). Some longitudinal PET investigations show that the rate of amyloid accumulation to follow-up has an inverted U relationship with baseline amyloid SUVR relative to cerebellar or brainstem/pons reference VOIs...
March 22, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28321471/feasibility-of-in-vivo-18-f-florbetaben-pet-mr-imaging-of-human-carotid-amyloid-%C3%AE
#4
Jan Bucerius, Henryk Barthel, Solveig Tiepolt, Peter Werner, Judith C Sluimer, Joachim E Wildberger, Marianne Patt, Swen Hesse, Hermann-Josef Gertz, Erik A L Biessen, Felix M Mottaghy, Osama Sabri
PURPOSE: Amyloid-beta (Aβ) peptides are involved in the inflammatory pathology of atherosclerosis. (18)F-Florbetaben is a PET tracer for clinical imaging of cerebral Aβ plaques in Alzheimer's disease (AD). We sought to determine whether specific uptake of (18)F-florbetaben in the carotid arteries can be identified using a fully integrated hybrid PET/MRI system and whether this uptake is associated with clinical cardiovascular disease (CVD) risk factors. METHODS: Carotid (18)F-florbetaben uptake was quantified as the mean of the maximum target-to-background ratio (meanTBRmax) in 40 cognitively impaired subjects (age 68...
March 21, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28320141/functional-magnetic-resonance-imaging-responses-in-cadasil
#5
Ikreet Cheema, Aaron R Switzer, Cheryl R McCreary, Michael D Hill, Richard Frayne, Bradley G Goodyear, Eric E Smith
OBJECTIVES: The magnitude of the blood oxygen dependent level (BOLD) functional MRI (fMRI) response to visual stimulation is reduced in the small vessel disease cerebral amyloid angiopathy (CAA), reflecting impaired vascular reactivity. We determined whether BOLD responses were reduced in another small vessel disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: BOLD fMRI data were collected using a visual stimulus (contrast-reversing checkerboard) and motor task (finger-tapping)...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28315374/glp-1-analogue-cjc-1131-prevents-amyloid-%C3%AE-protein-induced-impirments-of-spatial-memory-and-synaptic-plasticity-in-rats
#6
Sheng-Xiao Zhang, Hong-Yan Cai, Xiao-Wen Ma, Li Yuan, Jun Zhang, Zhao-Jun Wang, Yu-Feng Li, Jin-Shun Qi
Although amyloid β protein (Aβ) has been recognized as one of the main pathological characteristics in the brain of Alzheimer's disease (AD), the effective strategies against Aβ neurotoxicity are still deficient up to now. Glucagon-like peptide 1 (GLP-1), a natural gut hormone, was found to be effective in modulating insulin signaling and neural protection, but short half-life limited its clinical application in AD treatment. CJC-1131, a newly designed GLP-1 analogue with very longer half-life, has shown good effectiveness in the treatment of type 2 diabetes mellitus (T2DM)...
March 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28314118/in-vitro-assay-development-and-hts-of-small-molecule-human-abad-17%C3%AE-hsd10-inhibitors-as-therapeutics-in-alzheimer-s-disease
#7
Laura Aitken, Gemma Baillie, Andrew Pannifer, Angus Morrison, Philip S Jones, Terry K Smith, Stuart P McElroy, Frank J Gunn-Moore
A major hallmark of Alzheimer's disease (AD) is the formation of neurotoxic aggregates composed of the amyloid-β peptide (Aβ). Aβ has been recognized to interact with numerous proteins, resulting in pathological changes to the metabolism of patients with AD. One such mitochondrial metabolic enzyme is amyloid-binding alcohol dehydrogenase (ABAD), where altered enzyme function caused by the Aβ-ABAD interaction is known to cause mitochondrial distress and cytotoxic effects, providing a feasible therapeutic target for AD drug development...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28304302/sleep-deprivation-induced-plasma-amyloid-%C3%AE-transport-disturbance-in-healthy-young-adults
#8
Meng Wei, Beiyu Zhao, Kang Huo, Yongning Deng, Suhang Shang, Jie Liu, Yanbo Li, Louyan Ma, Yu Jiang, Liangjun Dang, Chen Chen, Shan Wei, Juanli Zhang, Hailei Yang, Fan Gao, Qiumin Qu
BACKGROUND: Sleep is an important physiological process and beneficial in the removal of brain metabolites and functional recovery. Prior studies have shown that sleep disorders are significant risk factors for Alzheimer's disease (AD). OBJECTIVE: The present study was designed to characterize the effect of short-term total sleep deprivation (TSD) on plasma amyloid-β (Aβ) concentrations. METHODS: A clinical trial was conducted between March 1, 2016, and April 1, 2016...
March 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28303360/modulation-of-linoleic-acid-binding-properties-of-human-serum-albumin-by-divalent-metal-cations
#9
Ekaterina L Nemashkalova, Eugene A Permyakov, Sergei E Permyakov, Ekaterina A Litus
Human serum albumin (HSA) is an abundant multiligand carrier protein, linked to progression of Alzheimer's disease (AD). Blood HSA serves as a depot of amyloid β (Aβ) peptide. Aβ peptide-buffering properties of HSA depend on interaction with its ligands. Some of the ligands, namely, linoleic acid (LA), zinc and copper ions are involved into AD progression. To clarify the interplay between LA and metal ion binding to HSA, the dependence of LA binding to HSA on Zn(2+), Cu(2+), Mg(2+) and Ca(2+) levels and structural consequences of these interactions have been explored...
March 16, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28303140/netosis-in-alzheimer-s-disease
#10
REVIEW
Enrica Caterina Pietronigro, Vittorina Della Bianca, Elena Zenaro, Gabriela Constantin
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive deterioration of cognitive functions. Its neuropathological features include amyloid-β (Aβ) accumulation, the formation of neurofibrillary tangles, and the loss of neurons and synapses. Neuroinflammation is a well-established feature of AD pathogenesis, and a better understanding of its mechanisms could facilitate the development of new therapeutic approaches. Recent studies in transgenic mouse models of AD have shown that neutrophils adhere to blood vessels and migrate inside the parenchyma...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28301218/retinal-pathology-is-associated-with-increased-blood-retina-barrier-permeability-in-a-diabetic-and-hypercholesterolaemic-pig-model-beneficial-effects-of-the-lppla2-inhibitor-darapladib
#11
Nimish K Acharya, Xin Qi, Eric L Goldwaser, George A Godsey, Hao Wu, Mary C Kosciuk, Theresa A Freeman, Colin H Macphee, Robert L Wilensky, Venkat Venkataraman, Robert G Nagele
Using a porcine model of diabetes mellitus and hypercholesterolaemia, we previously showed that diabetes mellitus and hypercholesterolaemia is associated with a chronic increase in blood-brain barrier permeability in the cerebral cortex, leading to selective binding of immunoglobulin G and deposition of amyloid-beta1-42 peptide in pyramidal neurons. Treatment with Darapladib (GlaxoSmithKline, SB480848), an inhibitor of lipoprotein-associated phospholipase-A2, alleviated these effects. Here, investigation of the effects of chronic diabetes mellitus and hypercholesterolaemia on the pig retina revealed a corresponding increased permeability of the blood-retina barrier coupled with a leak of plasma components into the retina, alterations in retinal architecture, selective IgG binding to neurons in the ganglion cell layer, thinning of retinal layers due to cell loss and increased glial fibrillary acidic protein expression in Müller cells, all of which were curtailed by treatment with Darapladib...
March 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28299725/defining-the-relationship-between-hypertension-cognitive-decline-and-dementia-a-review
#12
REVIEW
Keenan A Walker, Melinda C Power, Rebecca F Gottesman
Hypertension is a highly prevalent condition which has been established as a risk factor for cardiovascular and cerebrovascular disease. Although the understanding of the relationship between cardiocirculatory dysfunction and brain health has improved significantly over the last several decades, it is still unclear whether hypertension constitutes a potentially treatable risk factor for cognitive decline and dementia. While it is clear that hypertension can affect brain structure and function, recent findings suggest that the associations between blood pressure and brain health are complex and, in many cases, dependent on factors such as age, hypertension chronicity, and antihypertensive medication use...
March 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28298885/functional-roles-of-the-interaction-of-app-and-lipoprotein-receptors
#13
REVIEW
Theresa Pohlkamp, Catherine R Wasser, Joachim Herz
The biological fates of the key initiator of Alzheimer's disease (AD), the amyloid precursor protein (APP), and a family of lipoprotein receptors, the low-density lipoprotein (LDL) receptor-related proteins (LRPs) and their molecular roles in the neurodegenerative disease process are inseparably interwoven. Not only does APP bind tightly to the extracellular domains (ECDs) of several members of the LRP group, their intracellular portions are also connected through scaffolds like the one established by FE65 proteins and through interactions with adaptor proteins such as X11/Mint and Dab1...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28290668/surface-assay-for-specific-detection-of-soluble-amyloid-oligomers-utilizing-pronucleon-peptides-instead-of-antibodies
#14
Evgenia G Matveeva, Jonathan R Moll, Mariam M Khan, Richard B Thompson, Richard O Cliff
Immunoassays such as enzyme-linked immunosorbent assays (ELISAs) are widely used for diagnostics; however, antibodies as detection reagents may be insufficiently selective and have other shortcomings. We present a novel non-antibody-based detection method based on binding target molecules to peptides (used as recognition molecules): a surface assay for A-β oligomers employing a peptide comprising amino acid residues of the human β-amyloid protein (Pronucleon peptide) as the capture agent. For the sake of convenience, we term this the "Pronucleon peptide-linked immunosorbent assay", or PLISA...
March 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28289371/exosomes-origins-and-therapeutic-potential-for-neurodegenerative-disease
#15
REVIEW
Diana K Sarko, Cindy E McKinney
Exosomes, small lipid bilayer vesicles, are part of the transportable cell secretome that can be taken up by nearby recipient cells or can travel through the bloodstream to cells in distant organs. Selected cellular cytoplasm containing proteins, RNAs, and other macromolecules is packaged into secreted exosomes. This cargo has the potential to affect cellular function in either healthy or pathological ways. Exosomal content has been increasingly shown to assist in promoting pathways of neurodegeneration such as β-amyloid peptide (Aβ) accumulation forming amyloid plaques in the brains of patients with Alzheimer's disease, and pathological aggregates of proteins containing α-synuclein in Parkinson's disease transferred to the central nervous system via exosomes...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28288354/pharmacophore-based-3d-qsar-modeling-virtual-screening-and-docking-for-identification-of-potential-inhibitors-of-%C3%AE-secretase
#16
Ravichand Palakurti, Ramakrishna Vadrevu
The enzyme β-secretase-1 is responsible for the cleavage of the amyloid precursor protein, a vital step in the process of the formation of amyloid-β peptides which are known to lead to neurodegeneration causing Alzheimer's disease. Challenges associated with toxicity and blood brain permeation inability of potential inhibitors, continue to evade a successful therapy, thus demanding the search and development of highly active and effective inhibitors. Towards these efforts, we used a ligand based pharmacophore model generation from a dataset of known inhibitors whose activities against β-secretase hovered in the nano molar range...
March 6, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28285172/multifunctional-luv-liposomes-decorated-for-bbb-and-amyloid-targeting-b-in-vivo-brain-targeting-potential-in-wild-type-and-app-ps1-mice
#17
Konstantina Papadia, Anastasios D Giannou, Eleni Markoutsa, Christian Bigot, Greejte Vanhoute, Spyridon Mourtas, Annemie Van der Linded, Georgios T Stathopoulos, Sophia G Antimisiaris
Multifunctional liposomes (mf-LIPs) having a curcumin-lipid ligand (to target amyloids) together with two ligands to target the transferrin, and the low-density apolipoprotein receptor of the blood-brain-barrier (BBB) on their surface, were previously studied (in vitro) as potential theranostic systems for Alzheimer's disease (AD) (Papadia et al., 2017, Eur. J. Pharm. Sciences; 101:140-148). Herein, the targeting potential of mf-LIPs was compared to that of BBB-LIPs (liposomes having only the two BBB-specific ligands) in FVB mice (normal), as well as in double transgenic mice (APP/PS1) and their corresponding littermates (WT), by live-animal (in vivo) and explanted organ (ex vivo) imaging...
March 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28285163/the-effects-of-gold-nanoparticles-functionalized-with-%C3%A3-amyloid-specific-peptides-on-an-in-vitro-model-of-blood-brain-barrier
#18
Julie Ruff, Sabine Hüwel, M J Kogan, U Simon, H J Galla
We studied the effect of gold nanoparticle (AuNP) size, surface charge, concentration and morphology on the integrity of the Blood-Brain-Barrier (BBB) in a well-established in vitro model set-up. We focused on the effect of peptide functionalized hollow gold nanospheres and gold nanorods, which selectively bind to amyloidogenic β-amyloid structures. These AuNP conjugates have already been successfully tested as photothermal absorbers for potential application in Alzheimer's disease (AD) therapy in an in vitro set-up, but may exhibit a low passage through the BBB due to their overall negative charge...
March 8, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28285155/grape-powder-consumption-affects-the-expression-of-neurodegeneration-related-brain-proteins-in-rats-chronically-fed-a-high-fructose-high-fat-diet
#19
Hsiang Liao, Liang-Mao Chou, Yi-Wen Chien, Chi-Hao Wu, Jung-Su Chang, Ching-I Lin, Shyh-Hsiang Lin
Abnormal glucose metabolism in the brain is recognized to be associated with cognitive decline. Because grapes are rich in polyphenols that produce antioxidative and blood sugar-lowering effects, we investigated how grape consumption affects the expression and/or phosphorylation of neurodegeneration-related brain proteins in aged rats fed a high-fructose-high-fat (HFHF) diet. Wistar rats were maintained on the HFHF diet from the age of 8 weeks to 66 weeks, and then on an HFHF diet containing either 3% or 6% grape powder as an intervention for 12 weeks...
March 2, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28283595/astroglial-activation-and-altered-amyloid-metabolism-in-human-repetitive-concussion
#20
Pashtun Shahim, Yelverton Tegner, Niklas Marklund, Kina Höglund, Erik Portelius, David L Brody, Kaj Blennow, Henrik Zetterberg
OBJECTIVE: To determine whether postconcussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) is associated with CSF biomarker evidence of astroglial activation, amyloid deposition, and blood-brain barrier (BBB) impairment. METHODS: A total of 47 participants (28 professional athletes with PCS and 19 controls) were assessed with lumbar puncture (median 1.5 years, range 0.25-12 years after last concussion), standard MRI of the brain, and Rivermead Post-Concussion Symptoms Questionnaire (RPQ)...
March 10, 2017: Neurology
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