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David J Koss, Glynn Jones, Anna Cranston, Heidi Gardner, Nicholas M Kanaan, Bettina Platt
Post-mortem investigations of human Alzheimer's disease (AD) have largely failed to provide unequivocal evidence in support of the original amyloid cascade hypothesis, which postulated deposition of β-amyloid (Aβ) aggregates to be the cause of a demented state as well as inductive to tau neurofibrillary tangles (NFTs). Conflicting evidence suggests, however, that Aβ plaques and NFTs, albeit to a lesser extent, are present in a substantial subset of non-demented individuals. Hence, a range of soluble tau and Aβ species has more recently been implicated as the disease-relevant toxic entities...
October 21, 2016: Acta Neuropathologica
Richard A Armstrong, Ann C McKee, Victor E Alvarez, Nigel J Cairns
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder which may result from repetitive brain injury. A variety of tau-immunoreactive pathologies are present, including neurofibrillary tangles (NFT), neuropil threads (NT), dot-like grains (DLG), astrocytic tangles (AT), and occasional neuritic plaques (NP). In tauopathies, cellular inclusions in the cortex are clustered within specific laminae, the clusters being regularly distributed parallel to the pia mater. To determine whether a similar spatial pattern is present in CTE, clustering of the tau-immunoreactive pathology was studied in the cortex, hippocampus, and dentate gyrus in 11 cases of CTE and 7 cases of Alzheimer's disease neuropathologic change (ADNC) without CTE...
October 21, 2016: Journal of Neural Transmission
Tianfang Jiang, Qian Sun, Shengdi Chen
Oxidative stress reflects an imbalance between the overproduction and incorporation of free radicals and the dynamic ability of a biosystem to detoxify reactive intermediates. Free radicals produced by oxidative stress are one of the common features in several experimental models of diseases. Free radicals affect both the structure and function of neural cells, and contribute to a wide range of neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Although the precise mechanisms that result in the degeneration of neurons and the relevant pathological changes remain unclear, the crucial role of oxidative stress in the pathogenesis of neurodegenerative diseases is associated with several proteins (such as α-synuclein, DJ-1, Amyloid β and tau protein) and some signaling pathways (such as extracellular regulated protein kinases, phosphoinositide 3-kinase/Protein Kinase B pathway and extracellular signal-regulated kinases 1/2) that are tightly associated with the neural damage...
October 18, 2016: Progress in Neurobiology
A D Surowka, M Töpperwien, M Bernhardt, J D Nicolas, M Osterhoff, T Salditt, D Adamek, M Szczerbowska-Boruchowska
Human dopaminergic system in general, and substantia nigra (SN) neurons, in particular, are implicated in the pathologies underlying the human brain aging. The interplay between aberrations in the structural organization and elemental composition of SN neuron bodies has recently gained in importance as selected metals: Fe, Cu, Zn, Ca were found to trigger oxidative-stress-mediated aberration in their molecular assembly due to concomitant protein (alpha-synuclein, tau-protein) aggregation, gliosis and finally oxidative stress...
December 1, 2016: Talanta
Hanna F Skjåkødegård, Yngvild S Danielsen, Mette Morken, Sara-Rebekka F Linde, Rachel P Kolko, Katherine N Balantekin, Denise E Wilfley, Pétur B Júlíusson
BACKGROUND: The purpose of the FABO-study is to evaluate the effect of family-based behavioral social facilitation treatment (FBSFT), designed to target children's family and social support networks to enhance weight loss outcomes, compared to the standard treatment (treatment as usual, TAU) given to children and adolescents with obesity in a routine clinical practice. METHODS: Randomized controlled trial (RCT), in which families (n = 120) are recruited from the children and adolescents (ages 6-18 years) referred to the Obesity Outpatient Clinic (OOC), Haukeland University Hospital, Norway...
October 21, 2016: BMC Public Health
Marion T Turnbull, Elizabeth J Coulson
Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and are a major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in sporadic AD are unknown. Here we investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or a resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation...
October 20, 2016: Journal of Alzheimer's Disease: JAD
Qian Cai, Prasad Tammineni
Alzheimer's disease (AD) is characterized by brain deposition of amyloid plaques and tau neurofibrillary tangles along with steady cognitive decline. Synaptic damage, an early pathological event, correlates strongly with cognitive deficits and memory loss. Mitochondria are essential organelles for synaptic function. Neurons utilize specialized mechanisms to drive mitochondrial trafficking to synapses in which mitochondria buffer Ca2+ and serve as local energy sources by supplying ATP to sustain neurotransmitter release...
October 20, 2016: Journal of Alzheimer's Disease: JAD
N P Soumya, D N Das, S Jeyakumar, S Mondal, A Mor, U T Mundhe
Embryonic mortality is found to be the main source of reproductive wastage in domestic ruminants. Many genes are involved in the growth and development of the embryo, and the interferon-stimulated gene 15 (ISG 15) is one of the major gene stimulated by interferon tau, the maternal recognition of pregnancy signal in ruminants. In this study, both genomic and cDNA sequences of ISG 15 from Bos indicus (Deoni breed) were amplified and characterized. The genomic sequence of Deoni ISG 15 exhibited 99% identity with Bos taurus and 97% identity with that of Bos mutus and Bubalus bubalis...
October 21, 2016: Reproduction in Domestic Animals, Zuchthygiene
Nirbhay N Singh, Giulio E Lancioni, Bryan T Karazsia, Jeffrey Chan, Alan S W Winton
Caregivers of individuals with intellectual and developmental disabilities (IDD) often end up having their medical and psychological well-being compromised due to the stressful nature of caregiving, especially when those in their care engage in aggressive behavior. In this study, we provided caregivers with mindfulness-based training to enable them to better manage their psychological well-being and, through this, to also enhance specific indices of quality of life of the individuals in their care. Thus, the aim of the present study was to evaluate in a randomized controlled trial (RCT) the comparative effectiveness of Mindfulness-Based Positive Behavior Support (MBPBS) and Training-as-Usual (TAU) for caregivers in a congregate care facility for individuals with severe and profound IDD...
2016: Frontiers in Psychology
Andreas Hahn, Martin Schain, Maria Erlandsson, Petter Sjölin, Gregory M James, Olof T Strandberg, Douglas Hägerström, Rupert Lanzenberger, Jonas Jögi, Tomas G Olsson, Ruben Smith, Oskar Hansson
: Aggregation of hyperphosphorylated tau is a major hallmark of many neurodegenerative diseases, including Alzheimer's disease. In vivo imaging with positron emission tomography (PET) may offer important insights in pathophysiological mechanisms, diagnosis and disease progression. We describe different strategies for quantification of (18)F-AV1451 (T807) tau binding, including models with blood sampling and non-invasive alternatives. METHODS: 15 subjects (4 controls, 6 Alzheimer's disease (AD), 3 progressive supranuclear palsy (PSP), 2 cortico basal syndrome (CBS)) underwent 180 min PET with (18)F-AV1451 and arterial blood sampling...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Sumihiro Maeda, Lennart Mucke
Lasagna-Reeves et al. (2016) demonstrate that preventing the kinase Nuak1 from phosphorylating the microtubule-associated protein tau reduces the level of potentially pathogenic tau species in brain, a novel therapeutic strategy that could help counteract Alzheimer's disease and several other neurological disorders.
October 19, 2016: Neuron
Marek Sramko, Dan Wichterle, Josef Kautzner
This study evaluated hemodynamic feasibility and reproducibility of a new method for in vivo simulation of human atrial fibrillation (AF). The method was tested during sinus rhythm in 10 patients undergoing catheter ablation for AF. A simple electronic device was assembled that allowed triggering a cardiac stimulator by predefined series of RR intervals. Irregular RR interval sequences with a mean heart rate of 90/min and 130/min were obtained from ECG recordings of another patients with AF. Simultaneous atrioventricular pacing was delivered by catheters placed inside the coronary sinus and at the His bundle region...
2016: PloS One
Rui Gao, Guangjian Zhang, Xueqi Chen, Aimin Yang, Gwenn Smith, Dean F Wong, Yun Zhou
OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1-42 (Aβ1-42), phosphorylated tau (181P) (p-tau), and total tau (t-tau), have long been associated with the development of Parkinson disease (PD) and other neurodegenerative diseases. In this investigation, we reported the assessment of CSF biomarkers and their correlations with vesicular monoamine transporter 2 (VMAT2) bindings measured with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-AV133) that is being developed as a biomarker for PD...
2016: PloS One
Manuela Cristina Matesan, Saeed Elojeimy, Satoshi Minoshima
Molecular brain imaging I-FP-CIT SPECT is an important tool in evaluation of patients with parkinsonism. However, various neurodegenerative etiologies cannot be differentiated by I-FP-CIT SPECT alone. We present a case of progressive supranuclear palsy with abnormal I-FP-CIT SPECT and abnormal Tc-HMPAO SPECT depicted by quantitative analyses but unremarkable MRI 16 months after the onset of symptoms. Brain autopsy demonstrated presence of neuronal and glial tau pathology in both cortical and subcortical regions confirming the diagnosis of progressive supranuclear palsy...
October 18, 2016: Clinical Nuclear Medicine
Yu-Chao Zuo, Hong-Lian Li, Nan-Xiang Xiong, Jian-Ying Shen, Yi-Zhi Huang, Peng Fu, Hong-Yang Zhao
Nogo-66 plays a central role in the myelin-mediated inhibition of neurite outgrowth. Tau is a microtubule-associated protein involved in microtubule assembly and stabilization. It remains unverified whether tau interacts directly with growth factor receptors, or engages in cross-talk with regeneration inhibitors like Nogo-66. Here, we report that plasmid overexpression of tau significantly elevated the protein levels of total tau, phosphorylated tau, and microtubule-affinity regulating kinase (MARK). Nogo-66 transiently elevated the total tau protein level and persistently reduced the level of p-S262 tau (tau phosphorylated at serine 262), whereas it had little influence on the level of p-T205 tau (tau phosphorylated at threonine 205)...
October 19, 2016: Neuroscience Bulletin
FangFang, Hongyan Li, Tingting Qin, Min Li, Shiping Ma
The impaired insulin signaling has been recognized as a common pathogenetic mechanism between diabetes and Alzheimer's disease (AD). In the progression of AD, brain is characterized by defective insulin receptor substrate-1 (IRS-1) and increased oxidative stress. Thymol, a monoterpene phenol isolated from medicinal herbs, has exhibited robust neuroprotective effects. The present study was designed to investigate the protective effect of thymol on HFD-induced cognitive deficits, and explore the possible mechanisms...
October 20, 2016: Metabolic Brain Disease
Chih-Hsiang Hsu, Sheue-Er Wang, Ching-Lung Lin, Chun-Jen Hsiao, Shuenn-Jyi Sheu, Chung-Hsin Wu
In this study, we have reported the herbal formula B401 that has neuroprotective effects via multifunction, multitarget characteristics. It is possible that the herbal formula B401 may also provide new insights for AD. Here, we studied protective effects in the Tet-On Aβ42-GFP SH-SY5Y cell model and the APP/PS1/Tau triple transgenic mouse model by the herbal formula B401. In in vitro experiments, we showed that the herbal formula B401 treatment effectively reduces glutamate-induced excitotoxicity and acetylcholinesterase activity in Tet-On Aβ42-GFP SH-SY5Y cells...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Carlo Wilke, Frank Gillardon, Christian Deuschle, Markus A Hobert, Iris E Jansen, Florian G Metzger, Peter Heutink, Thomas Gasser, Walter Maetzler, Cornelis Blauwendraat, Matthis Synofzik
BACKGROUND AND OBJECTIVE: Reduced progranulin levels are a hallmark of frontotemporal dementia (FTD) caused by loss-of-function (LoF) mutations in the progranulin gene (GRN). However, alterations of central nervous progranulin expression also occur in neurodegenerative disorders unrelated to GRN mutations, such as Alzheimer's disease. We hypothesised that central nervous progranulin levels are also reduced in GRN-negative FTD. METHODS: Progranulin levels were determined in both cerebrospinal fluid (CSF) and serum in 75 subjects (37 FTD patients and 38 controls)...
October 20, 2016: Neuro-degenerative Diseases
Moran Frenkel-Pinter, Sharon Tal, Roni Scherzer-Attali, Malak Abu-Hussien, Idan Alyagor, Tal Eisenbaum, Ehud Gazit, Daniel Segal
Alzheimer's disease (AD) is the most abundant tauopathy and is characterized by Aβ-derived plaques and tau-derived tangles, resulting from the unfolding of the corresponding monomeric subunits into ordered β-sheet oligomers and fibrils. Intervening in the toxic aggregation process is a promising therapeutic approach, but, to date, a disease-modifying therapy is neither available for AD nor for other tauopathies. Along these lines, we have previously demonstrated that a small naphthoquinone-tryptophan hybrid, termed NQTrp, is an effective modulator of tauopathy in vitro and in vivo...
October 20, 2016: Neuro-degenerative Diseases
Lara Ordóñez-Gutiérrez, Adrián Posado-Fernández, Davoud Ahmadvand, Barbara Lettiero, Linping Wu, Marta Antón, Orfeu Flores, Seyed Moein Moghimi, Francisco Wandosell
The accumulation of extracellular amyloid-beta (Aβ) and intracellular neurofibrillary tangles (hyper-phosphorylated Tau) in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). Active and passive immunotherapy may limit cerebral Aβ deposition and/or accelerate its clearance. With the aid of a newly characterized monoclonal anti-Aβ antibody we constructed immunoPEGliposomes with high avidity for capturing Aβ in the periphery. The functionality of these vesicles in modulating Aβ uptake by both human brain capillary endothelial hCMEC/D3 cells (suppressing uptake) and THP-1 phagocytes (stimulating uptake) was confirmed in vitro...
August 2, 2016: Biomaterials
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