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https://www.readbyqxmd.com/read/27677546/increased-macrophage-intermediate-m1-m2-type-polarization-and-improved-cognition-in-mild-cognitive-impairment-patients-on-%C3%AF-3-supplementation
#1
Sam Famenini, Elizabeth A Rigali, Henry M Olivera-Perez, Johnny Dang, Michael To Chang, Ramesh Halder, Rammohan V Rao, Matteo Pellegrini, Verna Porter, Dale Bredesen, Milan Fiala
Monocyte/macrophages of patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) are defective in phagocytosis and degradation amyloid-β 1-42 (Aβ1-42), but are improved by ω-3 fatty acids (ω-3). The hypothesis of this study was that active Aβ1-42 phagocytosis by macrophages prevents brain amyloidosis and thus maintains cognition. We studied the effects of self-supplementation with a drink with ω-3, antioxidants, and resveratrol on Mini-Mental State Examination (MMSE) scores, macrophage M1M2 phenotype (the ratio of inflammatory CD54+CD80 and proresolution markers CD163+CD206), and Aβ1-42 phagocytosis in patients initially diagnosed as having MCI or subjective cognitive impairment (SCI)...
September 27, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27478073/dual-phase-high-temperature-membranes-for-co2-separation-performance-assessment-in-post-and-pre-combustion-processes
#2
Rahul Anantharaman, Thijs Peters, Wen Xing, Marie-Laure Fontaine, Rune Bredesen
Dual phase membranes are highly CO2-selective membranes with an operating temperature above 400 °C. The focus of this work is to quantify the potential of dual phase membranes in pre- and post-combustion CO2 capture processes. The process evaluations show that the dual phase membranes integrated with an NGCC power plant for CO2 capture are not competitive with the MEA process for post-combustion capture. However, dual phase membrane concepts outperform the reference Selexol technology for pre-combustion CO2 capture in an IGCC process...
October 20, 2016: Faraday Discussions
https://www.readbyqxmd.com/read/27294343/reversal-of-cognitive-decline-in-alzheimer-s-disease
#3
Dale E Bredesen, Edwin C Amos, Jonathan Canick, Mary Ackerley, Cyrus Raji, Milan Fiala, Jamila Ahdidan
Alzheimer's disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer's disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published [1]. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had had to discontinue work were able to return to work, and those struggling at work were able to improve their performance...
June 2016: Aging
https://www.readbyqxmd.com/read/27125172/effect-of-e-learning-program-on-risk-assessment-and-pressure-ulcer-classification-a-randomized-study
#4
Ida Marie Bredesen, Karen Bjøro, Lena Gunningberg, Dag Hofoss
BACKGROUND: Pressure ulcers (PUs) are a problem in health care. Staff competency is paramount to PU prevention. Education is essential to increase skills in pressure ulcer classification and risk assessment. Currently, no pressure ulcer learning programs are available in Norwegian. OBJECTIVES: Develop and test an e-learning program for assessment of pressure ulcer risk and pressure ulcer classification. METHODS: HASH(0x4fdd178) DESIGN, PARTICIPANTS AND SETTING: Forty-four nurses working in acute care hospital wards or nursing homes participated and were assigned randomly into two groups: an e-learning program group (intervention) and a traditional classroom lecture group (control)...
May 2016: Nurse Education Today
https://www.readbyqxmd.com/read/27060954/netrin-1-interrupts-amyloid-%C3%AE-amplification-increases-sa%C3%AE-pp%C3%AE-in-vitro-and-in-vivo-and-improves-cognition-in-a-mouse-model-of-alzheimer-s-disease
#5
Patricia R Spilman, Veronique Corset, Olivia Gorostiza, Karen S Poksay, Veronica Galvan, Junli Zhang, Rammohan Rao, Clare Peters-Libeu, Jon Vincelette, Andrew McGeehan, Melita Dvorak-Ewell, Janine Beyer, Jesus Campagna, Krystof Bankiewicz, Patrick Mehlen, Varghese John, Dale E Bredesen
Recent studies have shown that inoculation of susceptible mice with amyloid-β (Aβ) peptides accelerates Aβ deposition in the brain, supporting the idea that Aβ may be self-amplifying; however, the exact mechanism is not understood. Here we provide evidence that Aβ may self-amplify, in part, by inhibiting α-secretase ADAM10 (a disintegrin and metalloprotease) cleavage of full-length Aβ precursor protein (FL AβPP) and therefore allow greater β-secretase processing, and that Aβ itself is a substrate for ADAM10...
March 8, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/26870879/inhalational-alzheimer-s-disease-an-unrecognized-and-treatable-epidemic
#6
Dale E Bredesen
Alzheimer's disease is one of the most significant healthcare problems today, with a dire need for effective treatment. Identifying subtypes of Alzheimer's disease may aid in the development of therapeutics, and recently three different subtypes have been described: type 1 (inflammatory), type 2 (non-inflammatory or atrophic), and type 3 (cortical). Here I report that type 3 Alzheimer's disease is the result of exposure to specific toxins, and is most commonly inhalational (IAD), a phenotypic manifestation of chronic inflammatory response syndrome (CIRS), due to biotoxins such as mycotoxins...
February 2016: Aging
https://www.readbyqxmd.com/read/26791201/direct-transcriptional-effects-of-apolipoprotein-e
#7
Veena Theendakara, Clare A Peters-Libeu, Patricia Spilman, Karen S Poksay, Dale E Bredesen, Rammohan V Rao
A major unanswered question in biology and medicine is the mechanism by which the product of the apolipoprotein E ε4 allele, the lipid-binding protein apolipoprotein E4 (ApoE4), plays a pivotal role in processes as disparate as Alzheimer's disease (AD; in which it is the single most important genetic risk factor), atherosclerotic cardiovascular disease, Lewy body dementia, hominid evolution, and inflammation. Using a combination of neural cell lines, skin fibroblasts from AD patients, and ApoE targeted replacement mouse brains, we show in the present report that ApoE4 undergoes nuclear translocation, binds double-stranded DNA with high affinity (low nanomolar), and functions as a transcription factor...
January 20, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26770163/dale-e-bredesen-md-reversing-cognitive-decline
#8
Craig Gustafson
No abstract text is available yet for this article.
October 2015: Integrative Medicine
https://www.readbyqxmd.com/read/26343025/metabolic-profiling-distinguishes-three-subtypes-of-alzheimer-s-disease
#9
Dale E Bredesen
The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report that metabolic profiling reveals three Alzheimer's disease subtypes...
August 2015: Aging
https://www.readbyqxmd.com/read/26045577/hot-topics-in-research-preventive-neuroradiology-in-brain-aging-and-cognitive-decline
#10
REVIEW
C A Raji, H Eyre, S H Wei, D E Bredesen, S Moylan, M Law, G Small, P M Thompson, R M Friedlander, D H Silverman, B T Baune, T A Hoang, N Salamon, A W Toga, M W Vernooij
Preventive neuroradiology is a new concept supported by growing literature. The main rationale of preventive neuroradiology is the application of multimodal brain imaging toward early and subclinical detection of brain disease and subsequent preventive actions through identification of modifiable risk factors. An insightful example of this is in the area of age-related cognitive decline, mild cognitive impairment, and dementia with potentially modifiable risk factors such as obesity, diet, sleep, hypertension, diabetes, depression, supplementation, smoking, and physical activity...
October 2015: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/26041885/dynamic-self-guiding-analysis-of-alzheimer-s-disease
#11
REVIEW
Alexei Kurakin, Dale E Bredesen
We applied a self-guiding evolutionary algorithm to initiate the synthesis of the Alzheimer's disease-related data and literature. A protein interaction network associated with amyloid-beta precursor protein (APP) and a seed model that treats Alzheimer's disease as progressive dysregulation of APP-associated signaling were used as dynamic "guides" and structural "filters" in the recursive search, analysis, and assimilation of data to drive the evolution of the seed model in size, detail, and complexity. Analysis of data and literature across sub-disciplines and system-scale discovery platforms suggests a key role of dynamic cytoskeletal connectivity in the stability, plasticity, and performance of multicellular networks and architectures...
June 10, 2015: Oncotarget
https://www.readbyqxmd.com/read/25805829/%C3%AF-3-supplementation-increases-amyloid-%C3%AE-phagocytosis-and-resolvin-d1-in-patients-with-minor-cognitive-impairment
#12
Milan Fiala, Ramesh C Halder, Bien Sagong, Olivia Ross, James Sayre, Verna Porter, Dale E Bredesen
We investigated the effects of 4-17 month supplementation with ω-3 fatty acids and antioxidants (Smartfish drink; Smartfish AS, Oslo, Norway) in 12 patients with minor cognitive impairment (MCI) [minimental state examination (MMSE) ≥19], 2 patients with pre-MCI (normal MMSE), and 7 patients with Alzheimer disease (AD) (MMSE <19). We measured the phagocytosis of amyloid-β 1-42 (Aβ) by flow cytometry and microscopy, the transcription of inflammatory genes by RT-PCR, the production of resolvin D1 (RvD1) by enzyme immunoassay, and the cognitive status by MMSE...
July 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/25668572/correction-to-hunter-killer-peptide-hkp-for-targeted-therapy
#13
H Michael Ellerby, Dale E Bredesen, Satoshi Fujimura, Varghese John
No abstract text is available yet for this article.
February 26, 2015: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/25443301/the-prevalence-prevention-and-multilevel-variance-of-pressure-ulcers-in-norwegian-hospitals-a-cross-sectional-study
#14
Ida Marie Bredesen, Karen Bjøro, Lena Gunningberg, Dag Hofoss
BACKGROUND: Pressure ulcers are preventable adverse events. Organizational differences may influence the quality of prevention across wards and hospitals. OBJECTIVE: To investigate the prevalence of pressure ulcers, patient-related risk factors, the use of preventive measures and how much of the pressure ulcer variance is at patient, ward and hospital level. DESIGN: A cross-sectional study. SETTING: Six of the 11 invited hospitals in South-Eastern Norway agreed to participate...
January 2015: International Journal of Nursing Studies
https://www.readbyqxmd.com/read/25324467/reversal-of-cognitive-decline-a-novel-therapeutic-program
#15
Dale E Bredesen
This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD...
September 2014: Aging
https://www.readbyqxmd.com/read/25236395/essential-versus-accessory-aspects-of-cell-death-recommendations-of-the-nccd-2015
#16
REVIEW
L Galluzzi, J M Bravo-San Pedro, I Vitale, S A Aaronson, J M Abrams, D Adam, E S Alnemri, L Altucci, D Andrews, M Annicchiarico-Petruzzelli, E H Baehrecke, N G Bazan, M J Bertrand, K Bianchi, M V Blagosklonny, K Blomgren, C Borner, D E Bredesen, C Brenner, M Campanella, E Candi, F Cecconi, F K Chan, N S Chandel, E H Cheng, J E Chipuk, J A Cidlowski, A Ciechanover, T M Dawson, V L Dawson, V De Laurenzi, R De Maria, K-M Debatin, N Di Daniele, V M Dixit, B D Dynlacht, W S El-Deiry, G M Fimia, R A Flavell, S Fulda, C Garrido, M-L Gougeon, D R Green, H Gronemeyer, G Hajnoczky, J M Hardwick, M O Hengartner, H Ichijo, B Joseph, P J Jost, T Kaufmann, O Kepp, D J Klionsky, R A Knight, S Kumar, J J Lemasters, B Levine, A Linkermann, S A Lipton, R A Lockshin, C López-Otín, E Lugli, F Madeo, W Malorni, J-C Marine, S J Martin, J-C Martinou, J P Medema, P Meier, S Melino, N Mizushima, U Moll, C Muñoz-Pinedo, G Nuñez, A Oberst, T Panaretakis, J M Penninger, M E Peter, M Piacentini, P Pinton, J H Prehn, H Puthalakath, G A Rabinovich, K S Ravichandran, R Rizzuto, C M Rodrigues, D C Rubinsztein, T Rudel, Y Shi, H-U Simon, B R Stockwell, G Szabadkai, S W Tait, H L Tang, N Tavernarakis, Y Tsujimoto, T Vanden Berghe, P Vandenabeele, A Villunger, E F Wagner, H Walczak, E White, W G Wood, J Yuan, Z Zakeri, B Zhivotovsky, G Melino, G Kroemer
Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as 'accidental cell death' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. 'Regulated cell death' (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail...
January 2015: Cell Death and Differentiation
https://www.readbyqxmd.com/read/24958299/investigation-of-la1-xsrxcro3-%C3%A2-x-0-1-as-membrane-for-hydrogen-production
#17
Yngve Larring, Camilla Vigen, Florian Ahouanto, Marie-Laure Fontaine, Thijs Peters, Jens B Smith, Truls Norby, Rune Bredesen
Various inorganic membranes have demonstrated good capability to separate hydrogen from other gases at elevated temperatures. Hydrogen-permeable, dense, mixed proton-electron conducting ceramic oxides offer superior selectivity and thermal stability, but chemically robust candidates with higher ambipolar protonic and electronic conductivity are needed. In this work, we present for the first time the results of various investigations of La1-xSrxCrO3-∂ membranes for hydrogen production. We aim in particular to elucidate the material's complex transport properties, involving co-ionic transport of oxide ions and protons, in addition to electron holes...
2012: Membranes
https://www.readbyqxmd.com/read/24531152/paradoxical-effect-of-trka-inhibition-in-alzheimer-s-disease-models
#18
Qiang Zhang, Olivier Descamps, Matthew J Hart, Karen S Poksay, Patricia Spilman, Darci J Kane, Olivia Gorostiza, Varghese John, Dale E Bredesen
An unbiased screen for compounds that block amyloid-β protein precursor (AβPP) caspase cleavage identified ADDN-1351, which reduced AβPP-C31 by 90%. Target identification studies showed that ADDN-1351 is a TrkA inhibitor, and, in complementary studies, TrkA overexpression increased AβPP-C31 and cell death. TrkA was shown to interact with AβPP and suppress AβPP-mediated transcriptional activation. Moreover, treatment of PDAPP transgenic mice with the known TrkA inhibitor GW441756 increased sAβPPα and the sAβPPα to Aβ ratio...
2014: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/24389031/the-multi-functional-drug-tropisetron-binds-app-and-normalizes-cognition-in-a-murine-alzheimer-s-model
#19
Patricia Spilman, Olivier Descamps, Olivia Gorostiza, Clare Peters-Libeu, Karen S Poksay, Alexander Matalis, Jesus Campagna, Alexander Patent, Rammohan Rao, Varghese John, Dale E Bredesen
Tropisetron was identified in a screen for candidates that increase the ratio of the trophic, neurite-extending peptide sAPPα to the anti-trophic, neurite-retractive peptide Aβ, thus reversing this imbalance in Alzheimer's disease (AD). We describe here a hierarchical screening approach to identify such drug candidates, moving from cell lines to primary mouse hippocampal neuronal cultures to in vivo studies. By screening a clinical compound library in the primary assay using CHO-7W cells stably transfected with human APPwt, we identified tropisetron as a candidate that consistently increased sAPPα...
March 10, 2014: Brain Research
https://www.readbyqxmd.com/read/24145446/neuroprotective-sirtuin-ratio-reversed-by-apoe4
#20
Veena Theendakara, Alexander Patent, Clare A Peters Libeu, Brittany Philpot, Sonia Flores, Olivier Descamps, Karen S Poksay, Qiang Zhang, Gabriellee Cailing, Matthew Hart, Varghese John, Rammohan V Rao, Dale E Bredesen
The canonical pathogenesis of Alzheimer's disease links the expression of apolipoprotein E ε4 allele (ApoE) to amyloid precursor protein (APP) processing and Aβ peptide accumulation by a set of mechanisms that is incompletely defined. The development of a simple system that focuses not on a single variable but on multiple factors and pathways would be valuable both for dissecting the underlying mechanisms and for identifying candidate therapeutics. Here we show that, although both ApoE3 and ApoE4 associate with APP with nanomolar affinities, only ApoE4 significantly (i) reduces the ratio of soluble amyloid precursor protein alpha (sAPPα) to Aβ; (ii) reduces Sirtuin T1 (SirT1) expression, resulting in markedly differing ratios of neuroprotective SirT1 to neurotoxic SirT2; (iii) triggers Tau phosphorylation and APP phosphorylation; and (iv) induces programmed cell death...
November 5, 2013: Proceedings of the National Academy of Sciences of the United States of America
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