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https://www.readbyqxmd.com/read/29777753/characterization-of-impaired-cerebrovascular-structure-in-app-ps1-mouse-brains
#1
Kee-Chan Ahn, Cameron R Learman, Gary L Dunbar, Panchanan Maiti, Won-Cheoul Jang, Hyeon-Cheol Cha, Mee-Sook Song
Alzheimer's disease (AD) is defined by senile plaques, tauopathy and neuronal cell death in specific area of the brain. Recent studies suggest that neurovascular dysfunction may be an integral part of AD pathogenesis, contributing to the onset and development of AD pathologies such as neuronal death, inflammatory response, and breakdown of blood brain barrier (BBB). In addition, vascular complications caused by age-related metabolic diseases such as diabetes and high blood pressure have high incidence in development of dementia and AD...
May 16, 2018: Neuroscience
https://www.readbyqxmd.com/read/29777723/effect-of-acetylcholinesterase-inhibitors-donepezil-and-rivastigmine-on-the-activity-and-expression-of-cyclooxygenases-in-a-model-of-the-inflammatory-action-of-fluoride-on-macrophages-obtained-from-thp-1-monocytes
#2
Marta Goschorska, Irena Baranowska-Bosiacka, Izabela Gutowska, Maciej Tarnowski, Katarzyna Piotrowska, Emilia Metryka, Krzysztof Safranow, Dariusz Chlubek
Inflammation is an important factor in the development of many diseases of the central nervous system, including Alzheimer's disease and other types of dementia. ‪Given that acetylcholinesterase inhibitors are also currently believed to have anti-inflammatory properties, the purpose of this study was to investigate the effect of acetylcholinesterase inhibitors (rivastigmine, donepezil) on cyclooxygenase activity and expression using the proinflammatory action of fluoride (F- ) on cultured macrophages obtained from THP-1 monocytes...
May 16, 2018: Toxicology
https://www.readbyqxmd.com/read/29777707/functional-analysis-of-juxta-and-intra-membrane-domains-of-murine-app-by-genome-editing-in-neuro2a-cells
#3
Nanaka Kaneshiro, Ryosuke Imaoka, Masato Komai, Taku Kashiyama, Takashi Sakurai, Takashi Uehara, Nobumasa Takasugi
Amyloid-β precursor protein (APP) correlates with the pathogenesis of certain brain diseases, such as Alzheimer disease (AD). APP is cleaved by several enzymes to produce APP metabolites, including the amyloid beta peptide (Aβ), which accumulates in the brain of AD patients. However, the exact functions of APP metabolites remain elusive. In this study, using genome editing technology, we mutated juxta- and intra-membrane domains of murine APP in the mouse neuroblastoma cell line, Neuro2a. We identified several clones that expressed characteristic patterns of APP metabolites...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777699/cart-peptide-activates-the-nrf2-ho-1-antioxidant-pathway-and-protects-hippocampal-neurons-in-a-rat-model-of-alzheimer-s-disease
#4
Wenyu Jiao, Yongchen Wang, Linghong Kong, Tao Ou-Yang, Qing Meng, Qiang Fu, Zhenzhen Hu
The accumulation of amyloid-beta (Aβ) and oxidative stress damage in the brain are recognized as early features of Alzheimer's disease (AD). The cocaine- and amphetamine-regulated transcript (CART) peptide may possibly play an antioxidative role in neurons. The aim of this study was to investigate the potential antioxidant mechanism of CART peptide in a rat model of AD. We microinjected of Aβ1-42 (2μl/4μg/hemisphere) into rat hippocampus to set a rat model of AD. A pre-microinjection of CART peptide (1μl/0...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777524/mercury-involvement-in-neuronal-damage-and-in-neurodegenerative-diseases
#5
REVIEW
Veronica Lanza Cariccio, Annalisa Samà, Placido Bramanti, Emanuela Mazzon
Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis are characterized by a chronic and selective process of neuronal cell death. Although the causes of neurodegenerative diseases remain still unknown, it is now a well-established idea that more factors, such as genetic, endogenous, and environmental, are involved. Among environmental causes, the accumulation of mercury, a heavy metal considered a toxic agent, was largely studied as a probable factor involved in neurodegenerative disease course...
May 18, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29777097/gwas-on-family-history-of-alzheimer-s-disease
#6
Riccardo E Marioni, Sarah E Harris, Qian Zhang, Allan F McRae, Saskia P Hagenaars, W David Hill, Gail Davies, Craig W Ritchie, Catharine R Gale, John M Starr, Alison M Goate, David J Porteous, Jian Yang, Kathryn L Evans, Ian J Deary, Naomi R Wray, Peter M Visscher
Alzheimer's disease (AD) is a public health priority for the 21st century. Risk reduction currently revolves around lifestyle changes with much research trying to elucidate the biological underpinnings. We show that self-report of parental history of Alzheimer's dementia for case ascertainment in a genome-wide association study of 314,278 participants from UK Biobank (27,696 maternal cases, 14,338 paternal cases) is a valid proxy for an AD genetic study. After meta-analysing with published consortium data (n = 74,046 with 25,580 cases across the discovery and replication analyses), three new AD-associated loci (P < 5 × 10-8 ) are identified...
May 18, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29777037/inhibition-of-tbc1d5-activates-rab7a-and-can-enhance-the-function-of-the-retromer-cargo-selective-complex
#7
Matthew N J Seaman, Aamir S Mukadam, Sophia Y Breusegem
The retromer complex is a vital component of the endosomal protein sorting machinery being necessary for sorting into both the endosome-to-Golgi retrieval pathway and also the endosome-to-cell-surface recycling pathway. Retromer mediates cargo selection through a trimeric complex comprising VPS35, VPS29 and VPS26 which is recruited to endosomes by binding to Rab7a and Snx3. Retromer function is linked to two distinct neurodegenerative diseases, Parkinson's disease and Alzheimer's disease and modulating retromer function has been proposed as an avenue to explore for a putative therapy in these conditions...
May 18, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29777006/in-vivo-characterization-and-quantification-of-neurofibrillary-tau-pet-radioligand-18-f-mk-6240-in-humans-from-alzheimer-s-disease-dementia-to-young-controls
#8
Tobey J Betthauser, Karly A Cody, Matthew D Zammit, Dhanabalan Murali, Alexander K Converse, Todd E Barnhart, Charles K Stone, Howard A Rowley, Sterling C Johnson, Bradley T Christian
Tau positron emission tomography (PET) imaging has potential for elucidating changes in the deposition of neuropathological tau aggregates that are occurring during the progression of Alzheimer's disease (AD). This work investigates in vivo kinetics, quantification strategies and imaging characteristics of a novel tau PET radioligand [18 F]MK-6240 in humans. Methods: Fifty-one individuals ranging from cognitively normal young controls to persons with dementia underwent T1-weighted magnetic resonance imaging (MRI), and [11 C]PiB and [18 F]MK-6240 PET imaging...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29777003/impact-of-reference-target-region-selection-on-amyloid-pet-standard-uptake-value-ratios-in-the-phase-1b-prime-study-of-aducanumab
#9
Ping Chiao, Barry J Bedell, Brian Avants, Alex P Zijdenbos, Marilyn Grand'Maison, Paul O'Neill, John O'Gorman, Tianle Chen, Robert Koeppe
Standardized uptake value ratios (SUVRs) are commonly used to quantify tracer uptake in amyloid beta positron emission tomography (Aβ-PET). Here, we explore the impact of target and reference region of interest (ROI) selection on SUVR effect size using interventional data from the ongoing Phase Ib PRIME study (NCT01677572) of aducanumab (BIIB037) in patients with prodromal or mild Alzheimer's disease (AD). Methods: Florbetapir PET SUVR was calculated at baseline (screening) and Weeks 26 and 54 for patients randomized to placebo and each of four aducanumab doses (1, 3, 6, and 10 mg/kg), using whole cerebellum, cerebellar grey matter, cerebellar white matter, pons, and subcortical white matter as reference regions...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29776894/amyloid-pet-in-neurodegenerative-diseases-with-dementia
#10
V Camacho, A Gómez-Grande, P Sopena, D García-Solís, M Gómez Río, C Lorenzo, S Rubí, J Arbizu
Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive decline and memory loss, and is the most common form of dementia. Amyloid plaques with neurofibrillary tangles are a neuropathological hallmark of AD that produces synaptic dysfunction and culminates later in neuronal loss. Amyloid PET is a useful, available and non-invasive technique that provides in vivo information about the cortical amyloid burden. In the latest revised criteria for the diagnosis of AD biomarkers were defined and integrated: pathological and diagnostic biomarkers (increased retention on fibrillar amyloid PET or decreased Aβ1-42 and increased T-Tau or P-Tau in CSF) and neurodegeneration or topographical biomarkers (temporoparietal hypometabolism on 18 F-FDG PET and temporal atrophy on MRI)...
May 15, 2018: Revista Española de Medicina Nuclear e Imagen Molecular
https://www.readbyqxmd.com/read/29776741/a-small-diversity-library-of-%C3%AE-methyl-amide-analogs-of-sulindac-for-probing-anticancer-structure-activity-relationships
#11
Bini Mathew, Timothy S Snowden, Michele C Connelly, R Kiplin Guy, Robert C Reynolds
Non-steroidal anti-inflammatory drugs (NSAIDs) have a variety of potential indications that include management of pain and inflammation as well as chemoprevention and/or treatment of cancer. Furthermore, a specific form of ibuprofen, dexibuprofen or the S-(+) form, shows interesting neurological activities and has been proposed for the treatment of Alzheimer's disease. In a continuation of our work probing the anticancer activity of small sulindac libraries, we have prepared and screened a small diversity library of α-methyl substituted sulindac amides in the profen class...
May 10, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29776682/the-impact-of-apolipoprotein-e-alleles-on-cognitive-performance-in-patients-with-parkinson-s-disease
#12
Anna Pierzchlińska, Monika Białecka, Mateusz Kurzawski, Jarosław Sławek
Apolipoprotein E (ApoE) is a vital component of several lipoproteins and plays a major role in lipid metabolism. APOE gene comprises of three alleles determined by two single nucleotide polymorphisms (rs429358 and rs7412) resulting in the protein isoforms, among which ApoE4 is a confirmed risk factor for Alzheimer's Disease. However, the impact of APOE genotypes on Parkinson's Disease Dementia (PDD) is still inconclusive. The PDD diagnostic criteria are very inconsistent, and could be complemented with genetic factors...
May 5, 2018: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29775948/novel-3-phenylcoumarin-lipoic-acid-conjugates-as-multi-functional-agents-for-potential-treatment-of-alzheimer-s-disease
#13
Leili Jalili-Baleh, Hamid Nadri, Hamid Forootanfar, Alireza Samzadeh-Kermani, Tuba Tüylü Küçükkılınç, Beyza Ayazgok, Mahban Rahimifard, Maryam Baeeri, Mohsen Doostmohammadi, Loghman Firoozpour, Syed Nasir Abbas Bukhari, Mohammad Abdollahi, Mohammad Reza Ganjali, Saeed Emami, Mehdi Khoobi, Alireza Foroumadi
New series of triazole-containing 3-phenylcoumarin-lipoic acid conjugates were designed as multi-functional agents for treatment of Alzheimer's disease. The target compounds 4a-o were synthesized via the azide-alkyne cycloaddition reaction and their biological activities were primarily evaluated in terms of neuroprotection against H2 O2 -induced cell death in PC12 cells and AChE/BuChE inhibition. The promising compounds 4j and 4i containing four carbons spacer were selected for further biological evaluations...
May 2, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29775888/therapeutic-impact-of-rhuepo-on-abnormal-platelet-app-bace-1-presenilin-1-adam-10-and-a%C3%AE-expressions-in-chronic-kidney-disease-patients-with-cognitive-dysfunction-like-alzheimer-s-disease-a-pilot-study
#14
Vinothkumar G, Krishnakumar S, Sureshkumar, Shivashekar G, Sreedhar S, Preethikrishnan, Dinesh S, Sundaram A, Balakrishnan D, Riya, Venkataraman P
BACKGROUND: Cognitive dysfunction is reported to be a major cause of morbidity in chronic kidney disease (CKD). The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases . Platelets contain more than 95% of the circulating APP and implicate as a candidate biomarker for cognitive decline. Recombinant human erythropoietin (rHuEPO) is a standard therapy for anemia in CKD and also acts as a neuroprotective agent...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775635/enhanced-sampling-of-interdomain-motion-using-map-restrained-langevin-dynamics-and-nmr-application-to-pin1
#15
Jill J Bouchard, Junchao Xia, David A Case, Jeffrey W Peng
Many signaling proteins consist of globular domains connected by flexible linkers that allow for substantial domain motion. Because these domains often serve as complementary functional modules, the possibility of functionally important domain motions arises. To explore this possibility, we require knowledge of the ensemble of protein conformations sampled by interdomain motion. Measurements of NMR residual dipolar couplings (RDCs) of backbone NH bonds offer a per-residue characterization of interdomain dynamics, as the couplings are sensitive to domain orientation...
May 15, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29775624/characterization-and-comparative-analysis-of-a-new-mouse-microglial-cell-model-for-studying-neuroinflammatory-mechanisms-during-neurotoxic-insults
#16
Souvarish Sarkar, Emir Malovic, Deeksha Sarda, Vivek Lawana, Dharmin Rokad, Huajun Jin, Vellareddy Anantharam, Arthi Kanthasamy, Anumantha G Kanthasamy
Microglia are the first responders of the central nervous system, acting as the key modulators of neuroinflammation observed during neurotoxic insults as well as in the pathophysiology of several neurodegenerative disorders including Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD). The number of publications on microglia has increased steadily throughout the past decade because of immense interests in the neuroinflammation that precedes the neurodegenerative process. To study microglial biology and its role in modulating neuroinflammation, immortalized microglial cell lines derived from mice, rats, and humans have been developed...
May 15, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29775538/discovery-of-potent-and-centrally-active-6-substituted-5-fluoro-1-3-dihydro-oxazine-%C3%AE-secretase-bace1-inhibitors-via-active-conformation-stabilization
#17
Kenji Nakahara, Kouki Fuchino, Kazuo Komano, Naoya Asada, Genta Tadano, Tsuyoshi Hasegawa, Takahiko Yamamoto, Yusuke Sako, Masayoshi Ogawa, Chie Unemura, Motoko Hosono, Hisanori Ito, Gaku Sakaguchi, Shigeru Ando, Shuichi Ohnishi, Yasuto Kido, Tamio Fukushima, Deborah Dhuyvetter, Herman Borghys, Harrie J M Gijsen, Yoshinori Yamano, Yasuyoshi Iso, Ken-Ichi Kusakabe
β-Secretase (BACE1) has an essential role in the production of amyloid β peptides that accumulate in patients with Alzheimer's disease (AD). Thus, inhibition of BACE1 is considered to be a disease-modifying approach for the treatment of AD. Our hit-to-lead efforts led to a cellular potent 1,3-dihydro-oxazine 6, which however inhibited hERG and showed high P-gp efflux. The close analog of 5-fluoro-oxazine 8 reduced P-gp efflux; further introduction of electron withdrawing groups at the 6-position improved potency and also mitigated P-gp efflux and hERG inhibition...
May 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29775413/human-cerebral-collateral-arteriole-function-in-normal-cognition-mild-cognitive-impairment-and-dementia-subjects
#18
Raymond Q Migrino, Seth Truran, Nina Karamanova, Geidy Serrano, Calvin Madrigal, Hannah A Davies, Jillian Madine, Peter Reaven, Thomas G Beach
Clinical and preclinical studies suggest a link between cardiovascular disease and dementia disorders but the role of collateral brain circulation in cognitive dysfunction remains unknown. We aim to test the hypothesis that leptomeningeal arteriole (LMA) function and response to metabolic stressors differ among dementia, mild cognitive impairment (MCI) and normal cognition (CN) subjects. Following rapid autopsy, LMA were isolated from CN (N=10), MCI (N=12) or dementia subjects (N=42, Alzheimer's disease [AD], vascular dementia [VaD], or Other Dementia) and endothelial and smooth muscle-dependent function were measured at baseline and following exposure to β-amyloid (Aβ42 2 μM), palmitic acid (PA 150 μM) or medin (5μM) and compared...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29775277/cid-9998128-compound-is-a-potential-multi-target-drug-for-alzheimer-s-disease
#19
Nguyen Quoc Thai, Zuzana Bednarikova, Miroslav Gancar, Huynh Quang Linh, Chin-Kun Hu, Mai Suan Li, Zuzana Gazova
We have probed capability of small CID 9998128 compound as a potential multi-target drug for the Alzheimer's disease (AD) using in silico and in vitro experiments. By all-atom simulation and MM-PBSA method we have demonstrated that this compound strongly binds to both amyloid beta 42 (Aβ42 ) fibrils and β-secretase and the van der Waals interaction is dominating over the electrostatic interaction in binding affinity. A detailed analysis at the atomic level revealed that indazole in CID 99998128 structure made a major contribution to instability of all studied complexes...
May 18, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29775139/burden-and-strain-among-familial-caregivers-of-patients-with-dementia-in-china
#20
Min Zhang, Yu-Ping Chang, Yu Jin Liu, Ling Gao, Davina Porock
BACKGROUND: Alzheimer's disease is one of a variety of progressive and ultimately fatal neurodegenerative diseases that are characterized by a number of nervous and mental symptoms and behavior disorders. These problems are likely to cause burden and strain on caregivers. In this study, we demonstrated the level and relationship of burden and strain among caregivers of dementia patients in China. METHODS: A total of 212 caregivers of family members with dementia responded to the survey...
May 2018: Issues in Mental Health Nursing
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