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Daniela Hulcová, Kateřina Breiterová, Tomáš Siatka, Kamila Klímová, Lara Davani, Marcela Šafratová, Anna Hošťálková, Angela De Simone, Vincenza Andrisano, Lucie Cahlíková
Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine protein kinase that was originally identified as an enzyme involved in the control of glycogen metabolism. It plays a key role in diverse physiological processes including metabolism, the cell cycle, and gene expression by regulating a wide variety of well-known substances like glycogen synthase, tau-protein, and β-catenin. Recent studies have identified GSK-3β as a potential therapeutic target in Alzheimer´s disease, bipolar disorder, stroke, more than 15 types of cancer, and diabetes...
March 21, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Brandon P Vasquez, Jennifer C Tomaszczyk, Bhanu Sharma, Brenda Colella, Robin E A Green
BACKGROUND: Executive control deficits are deleterious and enduring consequences of moderate-severe traumatic brain injury (TBI) that disrupt everyday functioning. Clinically, such impairments can manifest as behavioural inconsistency, measurable experimentally by the degree of variability across trials of a reaction time (RT) task (also known as intraindividual variability [IIV]). Growing research on cognition after TBI points to cognitive deterioration in the chronic stages postinjury...
March 1, 2018: Neurorehabilitation and Neural Repair
Anette Søgaard Nielsen, Bent Nielsen
PURPOSE: Many patients with alcohol use disorder (AUD) fail to initiate outpatient treatment after being discharged from inpatient detoxification. The aim of the present study was to investigate the effect of outreach visits (OV) on subsequent attendance in outpatient AUD treatment. METHODS: Patients admitted to a detoxification unit at a mental health hospital were randomized to either referral as usual (TAU) or OV. OV involved a nurse from the outpatient clinic meeting the patients at the hospital and advising them about outpatient treatment, presenting an 'attendance contract' and offering a first appointment...
March 21, 2018: Nordic Journal of Psychiatry
Ahsan Habib, Huayan Hou, Takashi Mori, Jun Tian, Jin Zeng, Shengnuo Fan, Brian Giunta, Paul R Sanberg, Darrell Sawmiller, Jun Tan
Alzheimer's disease (AD) is an age-related disorder that affects cognition. Our previous studies showed that the neuroprotective fragment of amyloid procurer protein (APP) metabolite, soluble APPα (sAPPα), interferes with β-site APP-cleaving enzyme 1 (BACE1, β-secretase) cleavage and reduces amyloid-β (Aβ) generation. In an attempt to identify approaches to restore sAPPα levels, we found that human cord blood serum (CBS) significantly promotes sAPPα production compared with adult blood serum (ABS) and aged blood serum (AgBS) in Chinese hamster ovary cells stably expressing wild-type human APP...
January 1, 2018: Cell Transplantation
Balaji Krishnan, Rakez Kayed, Giulio Taglialatela
Introduction: Phospholipase D (PLD), a lipolytic enzyme that breaks down membrane phospholipids, is also involved in signaling mechanisms downstream of seven transmembrane receptors. Abnormally elevated levels of PLD activity are well-established in Alzheimer's disease (AD), implicating the two isoforms of mammalian phosphatidylcholine cleaving PLD (PC-PLD1 and PC-PLD2). Therefore, we took a systematic approach of investigating isoform-specific expression in human synaptosomes and further investigated the possibility of therapeutic intervention using preclinical studies...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Roger Mullins, David Reiter, Dimitrios Kapogiannis
Objective: Brain glucose hypometabolism is a prominent feature of Alzheimer's disease (AD), and in this case-control study we used Magnetic Resonance Spectroscopy (MRS) to assess AD-related differences in the posterior cingulate/precuneal ratio of glucose, lactate, and other metabolites. Methods: J-modulated Point-Resolved Spectroscopy (J-PRESS) and Prior-Knowledge Fitting (ProFit) software was used to measure glucose and other metabolites in the posterior cingulate/precuneus of 25 AD, 27 older controls, and 27 younger control participants...
March 2018: Annals of Clinical and Translational Neurology
Paloma Ruiz-Rodríguez, Antonio Cano-Vindel, Roger Muñoz-Navarro, Cristina M Wood, Leonardo A Medrano, Luciana Sofía Moretti
Introduction: In the primary care (PC) setting in Spain, the prevalence of emotional disorders (EDs) such as anxiety, depression and somatoform disorder is high. In PC patients, these disorders are not always managed in accordance with the recommendations provided by clinical practice guidelines, resulting in major direct and indirect economic costs and suboptimal treatment outcomes. The aim is to analyze and compare the cost-effectiveness and cost-utility of group-based psychological therapy versus treatment as usual (TAU)...
2018: Frontiers in Psychology
Steven A Harris, Elizabeth A Harris
This review focuses on research in the areas of epidemiology, neuropathology, molecular biology and genetics that implicates herpes simplex virus type 1 (HSV-1) as a causative agent in the pathogenesis of sporadic Alzheimer's disease (AD). Molecular mechanisms whereby HSV-1 induces AD-related pathophysiology and pathology, including neuronal production and accumulation of amyloid beta (Aβ), hyperphosphorylation of tau proteins, dysregulation of calcium homeostasis, and impaired autophagy, are discussed. HSV-1 causes additional AD pathologies through mechanisms that promote neuroinflammation, oxidative stress, mitochondrial damage, synaptic dysfunction, and neuronal apoptosis...
2018: Frontiers in Aging Neuroscience
José Ramón Alvero-Cruz, Jerónimo C García-Romero, Margarita Carrillo de Albornoz-Gil, Manuel Jiménez, Lorena Correas-Gomez, Piero Peñaloza, Iván López-Fernández, Elvis A Carnero
The main goal of this study was to analyze the longitudinal agreement between changes in trunk and abdominal adiposity variables assessed by DXA and portable bioimpedance device (ViScan). A total of 44 women, enrolled in a 4-month exercise intervention, were included in this analysis. Trunk/abdominal compartments were assessed by ViScan and DXA. Adjusted correlations for age and FM at first assessment (pre) were utilized to perform concurrent validation among methods and completed with an agreement analysis...
March 20, 2018: European Journal of Clinical Nutrition
Nancy R Stallings, Melissa A O'Neal, Jie Hu, Ege T Kavalali, Ilya Bezprozvanny, James S Malter
Early-stage Alzheimer's disease is characterized by the loss of dendritic spines in the neocortex of the brain. This phenomenon precedes tau pathology, plaque formation, and neurodegeneration and likely contributes to synaptic loss, memory impairment, and behavioral changes in patients. Studies suggest that dendritic spine loss is induced by soluble, multimeric amyloid-β (Aβ42 ), which, through postsynaptic signaling, activates the protein phosphatase calcineurin. We investigated how calcineurin caused spine pathology and found that the cis-trans prolyl isomerase Pin1 was a critical downstream target of Aβ42 -calcineurin signaling...
March 20, 2018: Science Signaling
Tanusree Sen, Pampa Saha, Nilkantha Sen
Acetylation of the microtubule-associated protein tau promotes its polymerization into neurofibrillary tangles that are implicated in the pathology of Alzheimer's disease (AD). The gaseous neurotransmitter nitric oxide (NO) regulates cell signaling through the nitrosylation of proteins. We found that NO production and tau acetylation at Lys280 occurred in the brain tissue in mice and in cultured mouse cortical neurons in response to exposure to amyloid-β1-42 (Aβ1-42 ), a peptide that is also implicated in AD...
March 20, 2018: Science Signaling
Joery Goossens, Maria Bjerke, Sara Van Mossevelde, Tobi Van den Bossche, Johan Goeman, Bart De Vil, Anne Sieben, Jean-Jacques Martin, Patrick Cras, Peter Paul De Deyn, Christine Van Broeckhoven, Julie van der Zee, Sebastiaan Engelborghs
BACKGROUND: We explored the diagnostic performance of cerebrospinal fluid (CSF) biomarkers in allowing differentiation between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD), as well as between FTLD pathological subtypes. METHODS: CSF levels of routine AD biomarkers (phosphorylated tau (p-tau181 ), total tau (t-tau), and amyloid-beta (Aβ)1-42 ) and neurofilament proteins, as well as progranulin levels in both CSF and serum were quantified in definite FTLD (n = 46), clinical AD (n = 45), and cognitively healthy controls (n = 20)...
March 20, 2018: Alzheimer's Research & Therapy
Inês Baldeiras, Isabel Santana, Maria João Leitão, Helena Gens, Rui Pascoal, Miguel Tábuas-Pereira, José Beato-Coelho, Diana Duro, Maria Rosário Almeida, Catarina Resende Oliveira
BACKGROUND: Cerebrospinal fluid (CSF) biomarkers have been used to increase the evidence of underlying Alzheimer's disease (AD) pathology in mild cognitive impairment (MCI). However, CSF biomarker-based classification often results in conflicting profiles with controversial prognostic value. Normalization of the CSF Aβ42 concentration to the level of total amyloid beta (Aβ), using the Aβ42/40 ratio, has been shown to improve the distinction between AD and non-AD dementia. Therefore, we evaluated whether the Aβ42/40 ratio would improve MCI categorization and more accurately predict progression to AD...
March 20, 2018: Alzheimer's Research & Therapy
Ross W Paterson, Catherine F Slattery, Teresa Poole, Jennifer M Nicholas, Nadia K Magdalinou, Jamie Toombs, Miles D Chapman, Michael P Lunn, Amanda J Heslegrave, Martha S Foiani, Philip S J Weston, Ashvini Keshavan, Jonathan D Rohrer, Martin N Rossor, Jason D Warren, Catherine J Mummery, Kaj Blennow, Nick C Fox, Henrik Zetterberg, Jonathan M Schott
BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are increasingly being used to support a diagnosis of Alzheimer's disease (AD). Their clinical utility for differentiating AD from non-AD neurodegenerative dementias, such as dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD), is less well established. We aimed to determine the diagnostic utility of an extended panel of CSF biomarkers to differentiate AD from a range of other neurodegenerative dementias. METHODS: We used immunoassays to measure conventional CSF markers of amyloid and tau pathology (amyloid beta (Aβ)1-42, total tau (T-tau), and phosphorylated tau (P-tau)) as well as amyloid processing (AβX-38, AβX-40, AβX-42, soluble amyloid precursor protein (sAPP)α, and sAPPβ), large fibre axonal degeneration (neurofilament light chain (NFL)), and neuroinflammation (YKL-40) in 245 patients with a variety of dementias and 30 controls...
March 20, 2018: Alzheimer's Research & Therapy
Hitoshi Okazawa
Tau phosphorylation has come into the limelight again, this time as a critical player in the earliest stages of dementia pathology. Mislocalization of phosphorylated tau to dendritic spines and the resultant degeneration of synapses are observed across multiple neurodegenerative diseases, even in the absence of tau aggregation. Moreover, other molecules phosphorylated by the same kinases, such as MARCKS, might contribute to ultra-early phase pathology by promoting synapse dysfunction.
March 20, 2018: ACS Chemical Neuroscience
Hiroshi Takahashi, Yasuchika Aoki, Arata Nakajima, Masato Sonobe, Fumiaki Terajima, Masahiko Saito, Takuya Miyamoto, Keita Koyama, Keiichiro Yamamoto, Takeo Furuya, Masao Koda, Seiji Ohtori, Masashi Yamazaki, Koichi Nakagawa
PURPOSE: To determine levels of biomarkers reflecting damage to axon, myelin, astrocytes, and neuron in cerebrospinal fluid (CSF) of patients with cervical compression myelopathy. METHODS: We collected 69 CSF samples from patients before spinal surgery for acutely worsening compression myelopathy (AM, 20), chronic compression myelopathy (CM, 20), and lumbar canal stenosis (LCS 29; control). We measured levels of phosphorylated neurofilament subunit H (pNF-H), tau (reflecting axonal damage), myelin basic protein (MBP) (reflecting demyelination), S100b (reflecting astrocyte damage), and neuron-specific enolase (NSE) (reflecting neuronal damage)...
March 19, 2018: European Spine Journal
Patricia Cristine Borck, Jean Franciesco Vettorazzi, Renato Chaves Souto Branco, Thiago Martins Batista, Junia Carolina Santos-Silva, Vanessa Yumi Nakanishi, Antonio Carlos Boschero, Rosane Aparecida Ribeiro, Everardo Magalhães Carneiro
The sulfur-containing amino acid, taurine (Tau), regulates glucose and lipid homeostasis under normal, pre- and diabetic conditions. Here, we aimed to verify whether Tau supplementation exerts its beneficial effects against obesity, hyperglycemia and alterations in islet functions, in leptin-deficient obese (ob/ob), over a long period of treatment. From weaning until 12 months of age, female ob/ob mice received, or not, 5% Tau in drinking water (obTau group). After this period, a reduction in hypertriglyceridemia and an improvement in glucose tolerance and insulin sensitivity were observed in obTau mice...
March 19, 2018: Amino Acids
Olga Press-Sandler, Yifat Miller
Amyloidogenic proteins are related to a variety of amyloid diseases, such as type 2 diabetes (T2D), Alzheimer's disease (AD) and Parkinson's disease (PD). The amyloid proteins in which this review focuses include amylin, Aβ, tau and α-synuclein. Understanding the molecular mechanisms in which these amyloidogenic proteins interact with membranes is a challenging research to both experimental and computational studies. This review illustrates recent studies on amyloid-membrane interactions, but it mainly focuses on the challenge issues related to experimental techniques to investigate at the molecular level these interactions and provides thoughts and outlook for future computational studies...
March 16, 2018: Biochimica et Biophysica Acta
Hanna Cho, Sang Won Seo, Jae Yong Choi, Hye Sun Lee, Young Hoon Ryu, Myung Sik Lee, Duk L Na, Hee Jin Kim, Chul Hyoung Lyoo
Behavioral variant frontotemporal dementia (bvFTD) is the most common form of frontotemporal dementia, and tau pathology can be found in 40%-50% of bvFTD patients. In this study, we sought to investigate18 F-flortaucipir-binding patterns and their correlates in clinically diagnosed bvFTD patients by comparing with results for Alzheimer's disease (AD) patients. We enrolled 20 bvFTD, 20 AD, and 20 age-matched healthy subjects who underwent neuropsychological tests, magnetic resonance imaging, and tau positron emission tomography scans with18 F-flortaucipir...
February 21, 2018: Neurobiology of Aging
K Imakawa, R Bai, K Kusama
During the peri-implantation period, ruminant conceptuses go through rapid elongation, followed by their attachment to the uterine endometrial epithelial cells, during which interferon-tau (IFNT), a trophectodermal cytokine required for the process of maternal recognition of pregnancy, is expressed in a temporal and spatial manner. On d 22 (d 0 = day of estrus), 2 to 3 d after the initiation of bovine conceptus attachment to the uterine epithelium, when IFNT production begins to subside, the expression of molecules related to epithelial-mesenchymal transition, zinc finger E-box binding homeobox 1, snail family transcriptional repressor 2, N-cadherin and vimentin was found in the trophectoderm...
March 15, 2018: Journal of Animal Science
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