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https://www.readbyqxmd.com/read/29166618/ipsc-based-compound-screening-and-in%C3%A2-vitro-trials-identify-a-synergistic-anti-amyloid-%C3%AE-combination-for-alzheimer-s-disease
#1
Takayuki Kondo, Keiko Imamura, Misato Funayama, Kayoko Tsukita, Michiyo Miyake, Akira Ohta, Knut Woltjen, Masato Nakagawa, Takashi Asada, Tetsuaki Arai, Shinobu Kawakatsu, Yuishin Izumi, Ryuji Kaji, Nobuhisa Iwata, Haruhisa Inoue
In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer's disease (AD). Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ), a pathogenic molecule in AD, and screened a pharmaceutical compound library...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166468/lafora-and-tr%C3%A3-tiakoff-the-naming-of-the-inclusion-bodies-discovered-by-lewy
#2
Eliasz Engelhardt
Fritz Heinrich Jakob Lewy described, for the first time, in 1912, novel peculiar inclusions in neurons of certain brain nuclei in patients with Paralysis agitans, and compared his finding to the amyloid bodies described by Lafora one year before. Gonzalo Rodriguez Lafora studied one patient with Paralysis agitans, in 1913, and recognized, described, and depicted structures identical to those previously reported by Lewy. He was the first to acknowledge Lewy's finding, and also the first to name such inclusions after the discoverer - cuerpos intracelulares de Lewy (Lewy bodies)...
October 2017: Arquivos de Neuro-psiquiatria
https://www.readbyqxmd.com/read/29166002/structure-and-affinity-of-cu-i-bound-to-human-serum-albumin
#3
Madison Sendzik, M Jake Pushie, Ewelina Stefaniak, Kathryn L Haas
Human serum albumin (HSA) is a major Cu carrier in human blood and in cerebrospinal fluid. A major assumption is that Cu bound to HSA is in the Cu(II) oxidation state; thus, interactions between HSA and Cu(II) have been intensely investigated for over four decades. HSA has been reported previously to support the reduction of Cu(II) to the Cu(I) oxidation state in the presence of the weak reductant, ascorbate; however, the interactions between HSA and Cu(I) have not been explicitly investigated. Here, we characterize both the apparent affinity of HSA for Cu(I) using solution competition experiments and the coordination structure of Cu(I) bound to HSA using X-ray absorption spectroscopy and in silico modeling...
November 22, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/29165985/nanoscale-dynamics-of-amyloid-beta-42-oligomers-as-revealed-by-high-speed-atomic-force-microscopy
#4
Siddhartha Banerjee, Zhiqiang Sun, Eric Y Hayden, David B Teplow, Yuri L Lyubchenko
Amyloid β-protein (Aβ) oligomers are emerging as potent neurotoxic species in Alzheimer's disease pathogenesis. Detailed characterization of oligomer structure and dynamics are necessary to develop oligomer-specific therapeutic agents. However, oligomers exist transiently, which complicates their structural analysis. One approach to mitigate these problems has been photochemical cross-linking of native oligomers. In these states, the oligomers can be isolated and purified for physical and chemical studies...
November 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/29165354/the-role-of-glucagon-like-peptide-1-glp1-in-type-3-diabetes-glp-1-controls-insulin-resistance-neuroinflammation-and-neurogenesis-in-the-brain
#5
REVIEW
Choon Sang Bae, Juhyun Song
Alzheimer's disease (AD), characterized by the aggregation of amyloid-β (Aβ) protein and neuroinflammation, is the most common neurodegenerative disease globally. Previous studies have reported that some AD patients show impaired glucose utilization in brain, leading to cognitive decline. Recently, diabetes-induced dementia has been called "type 3 diabetes", based on features in common with those of type 2 diabetes and the progression of AD. Impaired glucose uptake and insulin resistance in the brain are important issues in type 3 diabetes, because these problems ultimately aggravate memory dysfunction in the brain...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29164945/cardiovascular-complications-of-multiple-myeloma-in-the-elderly
#6
Pankaj Mathur, Sharmilan Thanendrarajan, Hakan Paydak, Srikanth Vallurupalli, Kedar Jambhekar, Sabha Bhatti, Carolina D Schinke, Faith E Davies, Jawahar L Mehta
Multiple myeloma is a malignant neoplasm characterized by plasma cell proliferation in blood and bone marrow. Approximately two-thirds of the patients with multiple myeloma are >65 years at the time of diagnosis. Patients in this age group often have co-existing cardiovascular diseases. Areas covered: The presence of multiple myeloma adds to the malady by direct deposition of amyloid protein in the heart or via toxicity of chemotherapeutic agents. Cardiac contractile dysfunction, arrhythmias and thromboembolic disorders are the main issues in the management of elderly patients with multiple myeloma...
November 22, 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/29164798/regionally-specific-changes-in-the-hippocampal-circuitry-accompany-progression-of-cerebrospinal-fluid-biomarkers-in-preclinical-alzheimer-s-disease
#7
Christine L Tardif, Gabriel A Devenyi, Robert S C Amaral, Sandra Pelleieux, Judes Poirier, Pedro Rosa-Neto, John Breitner, M Mallar Chakravarty
Neuropathological and in vivo brain imaging studies agree that the cornu ammonis 1 and subiculum subfields of the hippocampus are most vulnerable to atrophy in the prodromal phases of Alzheimer's disease (AD). However, there has been limited investigation of the structural integrity of the components of the hippocampal circuit, including subfields and extra-hippocampal white matter structure, in relation to the progression of well-accepted cerebrospinal fluid (CSF) biomarkers of AD, amyloid-β 1-42 (Aβ) and total-tau (tau)...
November 21, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/29164616/protection-against-%C3%AE-amyloid-neurotoxicity-by-a-non-toxic-endogenous-n-terminal-%C3%AE-amyloid-fragment-and-its-active-hexapeptide-core-sequence
#8
Kelly H Forest, Naghum Alfulaij, Komal Arora, Ruth Taketa, Tessi Sherrin, Cedomir Todorovic, James L M Lawrence, Gene T Yoshikawa, Ho-Leung Ng, Victor J Hruby, Robert A Nichols
High levels (μM) of beta amyloid (Aβ) oligomers are known to trigger neurotoxic effects, leading to synaptic impairment, behavioral deficits and apoptotic cell death. The hydrophobic C-terminal domain of Aβ, together with sequences critical for oligomer formation, is essential for this neurotoxicity. However, Aβ at low levels (pM-nM) has been shown to function as a positive neuromodulator and this activity resides in the hydrophilic N-terminal domain of Aβ. An N-terminal Aβ fragment (1-15/16), found in cerebrospinal fluid, was also shown to be a highly active neuromodulator and to reverse Aβ-induced impairments of long-term potentiation...
November 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29164603/18f-pet-with-florbetapir-for-the-early-diagnosis-of-alzheimer-s-disease-dementia-and-other-dementias-in-people-with-mild-cognitive-impairment-mci
#9
REVIEW
Gabriel Martínez, Robin Wm Vernooij, Paulina Fuentes Padilla, Javier Zamora, Xavier Bonfill Cosp, Leon Flicker
BACKGROUND: (18)F-florbetapir uptake by brain tissue measured by positron emission tomography (PET) is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using amyloid biomarkers tests like (18)F-florbetapir...
November 22, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29164602/18f-pet-with-flutemetamol-for-the-early-diagnosis-of-alzheimer-s-disease-dementia-and-other-dementias-in-people-with-mild-cognitive-impairment-mci
#10
REVIEW
Gabriel Martínez, Robin Wm Vernooij, Paulina Fuentes Padilla, Javier Zamora, Leon Flicker, Xavier Bonfill Cosp
BACKGROUND: (18)F-flutemetamol uptake by brain tissue, measured by positron emission tomography (PET), is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and the confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using some amyloid biomarkers tests like (18)F-flutemetamol...
November 22, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29164600/18f-pet-with-florbetaben-for-the-early-diagnosis-of-alzheimer-s-disease-dementia-and-other-dementias-in-people-with-mild-cognitive-impairment-mci
#11
REVIEW
Gabriel Martínez, Robin Wm Vernooij, Paulina Fuentes Padilla, Javier Zamora, Leon Flicker, Xavier Bonfill Cosp
BACKGROUND: (18)F-florbetaben uptake by brain tissue, measured by positron emission tomography (PET), is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using some amyloid biomarkers tests like (18)F-florbetaben...
November 22, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29164474/microcystic-calcifying-epithelial-odontogenic-tumor
#12
Celeste Sánchez-Romero, Román Carlos, Oslei Paes de Almeida, Mário José Romañach
Microcystic variant of calcifying epithelial odontogenic tumor is rare. We herein describe an additional well-documented case of microcystic CEOT. The affected patient is a Guatemalan 42-year-old female with an expansile well-defined mixed radiolucent-radiopaque lesion located in the right posterior mandible. The lesion was associated to an unerupted third molar. Histopathologic examination revealed nests and cords of moderately pleomorphic, eosinophilic polyhedral epithelial cells surrounded by a fibromyxoid stroma...
November 21, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/29164193/two-step-kinetic-model-of-the-self-assembly-mechanism-for-diphenylalanine-micro-nanotube-formation
#13
M S Ishikawa, C Busch, M Motzkus, H Martinho, T Buckup
Peptide nanostructures compose a new class of materials that have gained attention due to their interesting properties. Among them, nanotubes of diphenylalanine (FF) and its analogues have been one of the most studied structures in the last few years. Their importance originates from the need to better understand the formation of β-amyloid fibrils which are associated with Alzheimer's disease. In this work, the FF self-assembly process was probed using time-resolved Raman microscopy. The changes in the Raman spectra are followed over time after injecting water into a FF-film until micro/nanotubes (MNTs) are formed...
November 22, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29164115/cross-sectional-associations-of-fatigue-with-cerebral-%C3%AE-amyloid-in-older-adults-at-risk-of-dementia
#14
Claudie Hooper, Philipe De Souto Barreto, Nicola Coley, Matteo Cesari, Pierre Payoux, Anne Sophie Salabert, Sandrine Andrieu, Bruno Vellas
Fatigue is a common symptom in the elderly and has also been associated with impaired cognition in older adults. Hence, we sought to explore the cross-sectional relationship between fatigue and cerebral β-amyloid (Aβ) in 269 elderly individuals reporting subjective memory complaints from the Multidomain Alzheimer Preventive Trial. Standard uptake value ratios (SUVRs) were generated by [(18)F] florbetapir positron emission tomography (PET) using the cerebellum as a reference. Cortical-to-cerebellar SUVRs (cortical-SUVRs) were obtained using the mean signal from the frontal cortex, temporal cortex, parietal cortex, precuneus, anterior cingulate, and posterior cingulate...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29163775/loss-of-sun2-promotes-the-progression-of-prostate-cancer-by-regulating-fatty-acid-oxidation
#15
Cheng Yajun, Ye Chen, Li Xiaosa, Wang Xiao, Chen Jia, Wang Zhong, Xu Bin
The role of Sun2 has been described by previous studies in various types of cancers, including breast cancer and lung cancer. However, its role and potential molecular mechanism in the progression of prostate cancer have not been fully elucidated. In the present study, we found that Sun2 expression was reduced in prostate cancer tissues compared with paired normal tissues, and that low expression of Sun2 was significantly correlated with Higher Gleason scores, postoperative T stage (pT), Lymph nodal invasion and Clinical pathological stages...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163761/e3-ligase-mahogunin-mgrn1-influences-amyloid-precursor-protein-maturation-and-secretion
#16
Stefano Benvegnù, Tina Wahle, Carlos G Dotti
Altered processing of the Amyloid Precursor Protein (APP) is a well-recognized central pathogenic mechanism in Alzheimer's Disease (AD), and regulation of APP processing is a major focus of research in the AD field. However, how age-associated cellular and molecular changes contribute to changes in the amyloidogenic processing of APP have not been extensively clarified so far. We here provide evidence that the processing of APP is influenced by the e3 ubiquitin ligase Mahogunin (MGRN1), a neuroprotective molecule whose levels decrease with aging...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163489/ameliorating-amyloid-%C3%AE-fibrils-triggered-inflammation-via-curcumin-loaded-polymeric-nanoconstructs
#17
Andrea Ameruoso, Roberto Palomba, Anna Lisa Palange, Antonio Cervadoro, Aeju Lee, Daniele Di Mascolo, Paolo Decuzzi
Inflammation is a common hallmark in several diseases, including atherosclerosis, cancer, obesity, and neurodegeneration. In Alzheimer's disease (AD), growing evidence directly correlates neuronal damage with inflammation of myeloid brain cells, such as microglia. Here, polymeric nanoparticles were engineered and characterized for the delivery of anti-inflammatory molecules to macrophages stimulated via direct incubation with amyloid-β fibers. 200 nm spherical polymeric nanoconstructs (SPNs) and 1,000 nm discoidal polymeric nanoconstructs (DPNs) were synthesized using poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and lipid chains as building blocks...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163213/effect-of-human-amnion-epithelial-cells-on-the-acute-inflammatory-response-in-fetal-sheep
#18
Alana Westover, Jacqueline M Melville, Courtney McDonald, Rebecca Lim, Graham Jenkin, Euan M Wallace, Timothy J Moss
Intra-amniotic (IA) lipopolysaccharide (LPS) injection in sheep induces inflammation in the fetus. Human amnion epithelial cells (hAECs) moderate the effect of IA LPS on fetal development, but their influence on the acute inflammatory response to IA LPS is unknown. We aimed to determine the effects of hAECs on the acute fetal inflammatory response to IA LPS. After surgical instrumentation at 116 days' gestation (d) ewes were randomized to 1 of 4 groups at 123 d: IA LPS (10 mg) and intravenous (IV) saline (n = 8), IA LPS and IV hAECs (n = 6), IA saline and IV saline (n = 5) or IA saline and IV hAECs (n = 5)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29163142/low-serum-phosphorus-correlates-with-cerebral-a%C3%AE-deposition-in-cognitively-impaired-subjects-results-from-the-kbase-study
#19
Jong-Chan Park, Sun-Ho Han, Min S Byun, Dahyun Yi, Jun Ho Lee, Kyua Park, Dong Young Lee, Inhee Mook-Jung
Alzheimer's disease (AD), characterized by progressive cognitive decline, is the most prevalent neurodegenerative disease in the elderly. Cerebral β-amyloid (Aβ) deposition is the major pathological hallmark of AD. Recent studies also have shown that the serum level of phosphorus correlates to the risk of incident dementia. To date, the linkage between cerebral Aβ deposition and the serum phosphorus level remains unknown. In this study, we analyzed the levels of serum phosphorus in 109 mild cognitive impairment (MCI) and 73 AD dementia (ADD) subjects...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29163138/perspective-insights-into-disease-progression-diagnostics-and-therapeutic-approaches-in-alzheimer-s-disease-a-judicious-update
#20
REVIEW
Arif Tasleem Jan, Mudsser Azam, Safikur Rahman, Angham M S Almigeiti, Duk Hwan Choi, Eun Ju Lee, Qazi Mohd Rizwanul Haq, Inho Choi
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive accumulation of β-amyloid fibrils and abnormal tau proteins in and outside of neurons. Representing a common form of dementia, aggravation of AD with age increases the morbidity rate among the elderly. Although, mutations in the ApoE4 act as potent risk factors for sporadic AD, familial AD arises through malfunctioning of APP, PSEN-1, and-2 genes. AD progresses through accumulation of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) in brain, which interfere with neuronal communication...
2017: Frontiers in Aging Neuroscience
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