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https://www.readbyqxmd.com/read/29334684/aberrant-connectivity-in-mild-cognitive-impairment-and-alzheimer-disease-revealed-by-multimodal-neuroimaging-data
#1
Qing Li, Xia Wu, Fufang Xie, Kewei Chen, Li Yao, Jiacai Zhang, Xiaojuan Guo, Rui Li
BACKGROUND: Making use of multimodal data simultaneously to understand the neural mechanism of mild cognitive impairment (MCI) has been in the focus nowadays. The simultaneous use of multimodal data can take advantage of each modality which may only provide the view of one specific aspect of the brain. OBJECTIVE: To this end, the present study used structural magnetic resonance imaging (sMRI), fluorodeoxyglucose positron emission tomography (FDG-PET) and florbetapir PET to reveal the integrated brain network between MCI and normal controls (NCs)...
January 13, 2018: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/29334579/implementation-of-18f-labeled-amyloid-brain-pet-imaging-biomarker-in-the-diagnosis-of-alzheimer-s-disease-first-hand-experience-in-thailand
#2
Tanyaluck Thientunyakit, Chakmeedaj Sethanandha, Weerasak Muangpaisan, Orasa Chawalparit, Kuntarat Arunrungvichian, Tossaporn Siriprapa, Thonnapong Thongpraparn, Rujaporn Chanachai, Juri Gelovani
No abstract text is available yet for this article.
February 2018: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/29334498/evidence-based-interpretation-of-amyloid-%C3%AE-pet-results-a-clinician-s-tool
#3
David Bergeron, Rik Ossenkoppele, Robert Jr Laforce
BACKGROUND: Amyloid-β positron emission tomography (PET) allows for in vivo detection of fibrillar amyloid plaques, a pathologic hallmark of Alzheimer's disease (AD). However, amyloid-β PET interpretation is limited by the imperfect correlation between PET and autopsy, and the fact that it is positive in about 20% to 30% of cognitively normal individuals and non-AD dementias, especially when older or carrying the ε4 allele of apolipoprotein E (ApoE4). When facing a positive amyloid PET, clinicians have to evaluate the probability of a pathologic false positive as well as the probability of amyloid positivity being age-related, comorbid to a primary non-AD dementia (clinicopathologic false positive)...
January 12, 2018: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/29334419/a-metallo-pro-drug-to-target-cu-ii-in-the-context-of-alzheimer-s-disease
#4
Amandine Conte-Daban, Vinita Ambike, Régis Guillot, Nicolas Delsuc, Clotilde Policar, Christelle Hureau
Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a Mn(II)-based superoxide dismutase mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target Cu(II) associated events, i.e. Cu(II)-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-beta (Abeta) peptide aggregation. Complex 1+ is able to remove Cu(II) from Abeta, stop ROS and prevent alteration of Abeta aggregation as would do the corresponding free ligand LH. Using 1+ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity...
January 15, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29334222/on-line-preconcentration-in-capillaries-by-multiple-large-volume-sample-stacking-an-alternative-to-immunoassays-for-quantification-of-amyloid-beta-peptides-biomarkers-in-cerebrospinal-fluid
#5
Cedric Crosnier de Lassichere, Thanh Duc Mai, Markus Otto, Myriam Taverna
A novel electrokinetic preconcentration approach, so-called multiple pressure-assisted large-volume sample stacking with an electroosmotic flow pump (M-PA-LVSEP), was developed to allow in-capillary enrichment and separation of analytes from unlimited sample volumes. With this approach, the inherent limitation of in-capillary electrokinetic preconcentrations to the separation capillary volume can be overcome. The M-PA-LVSEP protocol relies on repeated cycles of pressure-assisted electroosmotic pumping and injection of extremely large sample volumes for analyte stacking and sample matrix removal...
January 15, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29333090/gene-and-protein-expression-profiles-in-a-mouse-model-of-collagen-induced-arthritis
#6
Sun-Yeong Gwon, Ki-Jong Rhee, Ho Joong Sung
The risk of rheumatoid arthritis (RA), an autoimmune disease, in the elderly population increases along with that of atherosclerosis, cardiovascular disease, type 2 diabetes, and Alzheimer's disease. Identifying specific biomarkers for RA can clarify the underlying molecular mechanisms and can aid diagnosis and patient care. To this end, the present study investigated the genes and proteins that are differentially expressed in RA using a mouse collagen-induced arthritis (CIA) model. We performed gene microarray and proteome array analyses using blood samples from the mice and found that 50 genes and 24 proteins were upregulated and 48 genes were downregulated by more than 2-fold in the CIA model relative to the control...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29332926/differentiating-between-alzheimer-disease-patients-and-controls-with-phase-difference-enhanced-imaging-at-3t-a-feasibility-study
#7
Machiko Tateishi, Mika Kitajima, Toshinori Hirai, Tetsuya Yoneda, Mamoru Hashimoto, Nan Kurehana, Hiroyuki Uetani, Ryuji Fukuhara, Minako Azuma, Yasuyuki Yamashita
PURPOSE: To test the feasibility of the phase difference enhanced (PADRE) imaging for differentiation between Alzheimer disease (AD) patients and control subjects on 3T MR imaging. MATERIALS AND METHODS: Fifteen patients with AD and 10 age-matched control subjects underwent two-dimensional fast field echo imaging to obtain PADRE images on a 3T MR scanner. A double Gaussian distribution model was used to determine the threshold phase value for differentiation between the physiologic and non-physiologic iron in the cerebral cortices, and PADRE images were processed with the threshold...
January 15, 2018: Magnetic Resonance in Medical Sciences: MRMS
https://www.readbyqxmd.com/read/29332593/facile-synthesis-crystal-structure-dft-calculation-and-biological-activities-of-4-2-fluorophenyl-3-3-methoxybenzyl-1h-1-2-4-triazol-5-4h-one-5
#8
Muhammad Saleem, Muhammad Rafiq, Yeon Ki Jeong, Dae Won Cho, Chong-Hyeak Kim, Sung-Yum Seo, Chang-Shik Choi, Seong-Karp Hong, Ki-Hwan Lee
BACKGROUND: In the past few decades, the design, synthesis and characterization of novel heterocyclic compounds with auspicious biological profile received the considerable attention of scientific community. Among them, the small and simple organic molecular backbone like triazole moiety have broad spectrum of applications in the medicinal as well as diagnostic areas. OBJECTIVE: The objective of present study was the synthesis, characterization and exploration of biological profile of 4-(2-fluorophenyl)-3-(3-methoxybenzyl)-1H-1,2,4-triazol-5(4H)-one (5)...
January 12, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29332586/recent-developments-on-multi-target-directed-tacrines-for-alzheimer-s-disease-i-the-pyranotacrines
#9
Alejandro Romero, Jose Marco-Contelles
Tacrine was the first drug to displayed beneficial effects on cognitive impairment of Alzheimer disease (AD) patients. Unfortunately, many treated patients displayed related hepatotoxicity, and hence this drug was withdrawn. Notwithstanding, recent efforts have been directed to design small tacrine analogues targeting the underlying pathogenic mechanisms of AD. In this context, we have developed a number of pyranotacrines by changing the benzene fused ring in tacrine by a 4H-pyran. Based on this strategy, in this account we will show the tacrine analogues that we have designed, synthesized and evaluated as potential multipotent agents for AD in the last years...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29332585/new-tacrines-as-anti-alzheimer-s-disease-agents-ii-the-benzo-chromenopyranotacrines
#10
Maria J Oset-Gasque, Jose Marco-Contelles
Tacrine was the first drug approved by FDA (US) for the treatment of Alzheimer's disease suffering patients. Nowadays, this agent has been withdrawn from the clinics due to secondary effects, among them, and the most important, its hepatotoxicity. However, the research on new tacrine analogues devoid of these therapeutically undesirable effects, but benefiting of their high and well known positive cholinergic power, has produced a number of new non-hepatotoxic tacrines. In this context, in our laboratory, in the last years we have prepared a new heterocyclic tacrines by changing the benzene ring present in tacrine by appropriate heterocyclic motifs...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29332584/multicomponent-reactions-for-multitargeted-compounds-for-alzheimer-s-disease
#11
Lhassane Ismaili, Maria do Carmo Carreiras
Alzheimer's disease (AD) is a multifactorial and fatal neurodegenerative disorder affecting around 35 million people worldwide, which is characterized by decline of cholinergic function, deregulation of amyloid beta (Aβ) oligomers formation and Aβ fibril deposition. Multi-target--directed ligands (MTDLs) have emerged as an original strategy for developing new therapeutic agents on AD. Multicomponent reactions (MCRs) are a useful alternative to sequential multistep syntheses, allowing scaffold diversity and a rapid and easy access to biologically relevant compounds...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29332582/dual-bace-1-gsk-3%C3%AE-inhibitors-to-combat-alzheimer-s-disease-a-focus-review
#12
Angela Rampa, Silvia Gobbi, Rita Maria Concetta Di Martino, Federica Belluti, Alessandra Bisi
In industrialized countries, Alzheimer's disease represents the most devastating neurodegenerative disorder in elderly people and the search for a disease modifying agent is still justified by this unmet need. Several possible targets have been explored to find an appropriate drug therapy, and in this review dual inhibitors of beta secretase and glycogen synthase kinase 3, recently reported in literature, will be appraised. Applying a ligand-based approach, the triazinone core emerged as a suitable scaffold to simultaneously bind the aspartic dyad of BACE-1 and the ATP site of GSK-3β, leading to a series of small molecules endowed with a balanced micromolar affinity and a promising pharmacokinetic profile...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29332579/alzheimer-s-disease-a-systemic-review-of-substantial-therapeutic-targets-and-the-leading-multi-functional-molecules
#13
Tarana Umar, Nasimul Hoda
Alzheimer's disease (AD) is a fatal neurodegenerative disorder, having a complex aetiology with numerous possible drug targets. There are targets that have been known for years while more new targets and theories have also emerged. Beta amyloid and cholinesterases are the most significant biological targets for finding curative treatment of AD. The major class of drugs used for AD till now has been the Cholinesterase (ChE) inhibitors. Other prevailing models of molecular pathogenesis in AD include neurofibrillary tangles (NFTs) and amyloid deposition, tryptophan degradation pathway, kinase and phosphatase activity imbalance and neuroinflammation...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29332578/amyloid-%C3%AE-inhibits-pdgf%C3%AE-receptor-activation-and-prevents-pdgf-bb-induced-neuroprotection
#14
Hui Liu, Golam T Saffi, Maryam S Vasefi, Youngjik Choi, Jeff S Kruk, Nawaz Ahmed, Nyasha Gondora, John Mielke, Zoya Leonenko, Michael A Beazely
PDGFβ receptors and their ligand, PDGF-BB, are upregulated in vivo after neuronal insults such as ischemia. When applied exogenously, PDGF-BB is neuroprotective against excitotoxicity and HIV proteins. METHODS: Given this growth factor's neuroprotective ability, we sought to determine if PDGF-BB would be neuroprotective against amyloid-β (1-42), one of the pathological agents associated with Alzheimer's disease (AD). In both primary hippocampal neurons and the human-derived neuroblastoma cell line, SH-SY5Y, amyloid- treatment for 24 h decreased surviving cell number in a concentration-dependent manner...
January 9, 2018: Current Alzheimer Research
https://www.readbyqxmd.com/read/29332563/multi-target-directed-drugs-as-a-modern-approach-for-drug-design-towards-alzheimer-s-disease-an-update
#15
Matheus de Freitas Silva, Kris Simone Tranches Dias, Vanessa Silva Gontijo, Cindy Juliet Cristancho Ortiz, Claudio Viega
Alzheimer's disease (AD) is a progressive multifactorial neurodegenerative disorder. Currently, no effective treatment is available and this is due to multiple factors involved in pathophysiology and severity of AD. A recent approach for the rational design of new drug candidates, also called multitarget-directed ligands (MTDL) strategy, has been used to develop a variety of hybrid compounds capable to act simultaneously in diverse biological targets. The discovery of drug molecules capable of targeting multiple factors involved in AD pathogenesis would greatly facilitate in improving therapeutic strategies...
January 10, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29332554/evaluating-the-dose-dependent-mechanism-of-action-of-trazodone-by-estimation-of-occupancies-for-different-brain-neurotransmitter-targets
#16
Luca Settimo, David Taylor
Trazodone is a drug that was introduced in the clinic almost 40 years ago. It is licensed to treat depression, but it is also commonly used off-label to treat insomnia. A recent study shows that it could be promising in preventing neurodegeneration in mice, and clinical trials to assess its possible beneficial effects on dementia and Alzheimer's disease are expected to start soon in humans. In this study, we describe the dose-dependent pharmacology of trazodone by carrying out pharmacokinetic simulations aiming to predict the brain concentrations of trazodone for different drug-dosing regimens and calculating occupancy for 28 different targets for which published trazodone-binding data are available...
January 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29332053/apparent-cognitive-decline-as-revealed-by-an-executive-function-test-within-a-cohort-of-elderly-individuals-self-reporting-normal-cognitive-performance
#17
Thomas B Shea, Ruth Remington
Alzheimer's disease (AD) can be preceded by subtle memory decline that can last a decade or more before progressing to what would be diagnosed as the mild cognitive impairment stage. During this early stage of decline, individuals and even their caregivers can fail to perceive any serious difficulty or need to consult a physician. Herein, we present evidence in support of these concerns, and demonstrate how this can interfere not only with clinical trials of AD but also those involving cognitive performance of elderly individuals without intentional reference to AD...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332052/when-art-meets-gardens-does-it-enhance-the-benefits-the-nancy-hypothesis-of-care-for-persons-with-alzheimer-s-disease
#18
Thérèse Rivasseau Jonveaux, Reinhard Fescharek
The creation of healing gardens for persons with Alzheimer's disease and related diseases (ADRD) offers vast potential. They can play a role in the scaffolding of cognitive disorders, emotional stress, sensory processing, sense of harmony, and appeasement. These effects are achieved through a distributed interplay of psychological functions with the immediate environment and local culture on the one hand, and dialogue on the other. The garden, a natural canvas created by man, shares with art the ability to foster an esthetic sense for which the perception can be measured by functional neurological imaging exploration...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332049/free-heme-and-amyloid-%C3%AE-a-fatal-liaison-in-alzheimer-s-disease
#19
Elisabeth Chiziane, Henriette Telemann, Martin Krueger, Juliane Adler, Jürgen Arnhold, A Alia, Jörg Flemmig
While the etiology of Alzheimer's disease (AD) is still unknown, an increased formation of amyloid-β (Aβ) peptide and oxidative processes are major pathological mechanism of the disease. The interaction of Aβ with free heme leads to the formation of peroxidase-active Aβ-heme complexes. However, enzyme-kinetic data and systematic mutational studies are still missing. These aspects were addressed in this study to evaluate the role of Aβ-heme complexes in AD. The enzyme-kinetic measurements showed peroxidase-specific pH- and H2O2-dependencies...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332048/frequency-of-cardiovascular-genetic-risk-factors-in-a-calabrian-population-and-their-effects-on-dementia
#20
Raffaele Maletta, Nicoletta Smirne, Livia Bernardi, Maria Anfossi, Maura Gallo, Maria Elena Conidi, Rosanna Colao, Gianfranco Puccio, Sabrina A M Curcio, Valentina Laganà, Francesca Frangipane, Chiara Cupidi, Maria Mirabelli, Franca Vasso, Giusi Torchia, Maria G Muraca, Raffaele Di Lorenzo, Giuseppina Rose, Alberto Montesanto, Giuseppe Passarino, Amalia C Bruni
BACKGROUND: Several genetic variants playing a key role in cholesterol levels, blood pressure, and vascular dysfunction influence the risk of Alzheimer's disease (AD) and vascular dementia (VaD). The many meta-analysis studies carried out on large numbers of samples in different populations have not provided clear results to date, because a trans-ethnic shift of risk genotypes in different populations is often observed. OBJECTIVES: To determine genotypes allele frequencies of the polymorphisms most frequently identified to be correlated with cardio-cerebrovascular disease and AD in a Southern Italy population and to investigate their possible association with dementia...
2018: Journal of Alzheimer's Disease: JAD
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