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https://www.readbyqxmd.com/read/28222529/progressive-motor-deficit-is-mediated-by-the-denervation-of-neuromuscular-junctions-and-axonal-degeneration-in-transgenic-mice-expressing-mutant-p301s-tau-protein
#1
Zhuoran Yin, Femke Valkenburg, Betty E Hornix, Ietje Mantingh-Otter, Xingdong Zhou, Muriel Mari, Fulvio Reggiori, Debby Van Dam, Bart J L Eggen, Peter P De Deyn, Erik Boddeke
Tauopathies include a variety of neurodegenerative diseases associated with the pathological aggregation of hyperphosphorylated tau, resulting in progressive cognitive decline and motor impairment. The underlying mechanism for motor deficits related to tauopathy is not yet fully understood. Here, we use a novel transgenic tau mouse line, Tau 58/4, with enhanced neuron-specific expression of P301S mutant tau to investigate the motor abnormalities in association with the peripheral nervous system. Using stationary beam, gait, and rotarod tests, motor deficits were found in Tau 58/4 mice already 3 months after birth, which deteriorated during aging...
February 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28222507/recent-progress-in-alzheimer-s-disease-research-part-1-pathology
#2
Francis T Hane, Brenda Y Lee, Zoya Leonenko
The field of Alzheimer's disease (AD) research has grown exponentially over the past few decades, especially since the isolation and identification of amyloid-β from postmortem examination of the brains of AD patients. Recently, the Journal of Alzheimer's Disease (JAD) put forth approximately 300 research reports which were deemed to be the most influential research reports in the field of AD since 2010. JAD readers were asked to vote on these most influential reports. In this 3-part review, we review the results of the 300 most influential AD research reports to provide JAD readers with a readily accessible, yet comprehensive review of the state of contemporary research...
February 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28222506/synaptic-compensation-as-a-probable-cause-of-prolonged-mild-cognitive-impairment-in-alzheimer-s-disease-implications-from-a-transgenic-mouse-model-of-the-disease
#3
Narjes Baazaoui, Michael Flory, Khalid Iqbal
Alzheimer's disease (AD) is a slow, progressive neurodegenerative disease in which cognitive decline takes place over a period of several years with a very variable period of mild cognitive impairment (MCI) and, in some cases, relatively long period before progression to dementia. The cognitive deficit during MCI is probably due to neuronal loss, an intermediate level of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT) and synaptosis, which is interrupted with a transient compensatory increase. We found impairment in reference memory accompanied by a decrease in the expression of synaptophysin, β-III tubulin, and MAP2 and a trend for GluR1, at 12 weeks of age in 3xTg-AD mice (hAPPSwe, P301L tau, PS1 [M146V] knock-in), a widely used transgenic model of AD...
February 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28222302/how-to-handle-adsorption-of-cerebrospinal-fluid-amyloid-%C3%AE-1-42-in-laboratory-practice-identifying-problematic-handlings-and-resolving-the-issue-by-use-of-the-a%C3%AE-42-a%C3%AE-40-ratio
#4
Eline Willemse, Kees van Uffelen, Britta Brix, Sebastiaan Engelborghs, Hugo Vanderstichele, Charlotte Teunissen
INTRODUCTION: We aimed to investigate factors defining amyloid-β (1-42) (Aβ1-42) adsorption during preanalytical workup of cerebrospinal fluid (CSF). METHODS: CSF was transferred to new tubes ≤4 times. Variables tested were different polypropylene tube brands, volumes, CSF Aβ1-42 concentrations, incubation times, pipettes, vortex intensities, and other CSF proteins, including hyperphosphorylated tau and IL-1RAcP. An enquiry assessed the number of transfers in current practice...
February 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28222213/rab7a-regulates-tau-secretion
#5
Lilia Rodriguez, Nguyen-Vi Mohamed, Alexandre Desjardins, Roger Lippé, Edward Fon, Nicole Leclerc
The axonal microtubule-associated protein TAU, involved in Alzheimer's disease (AD), can be found in the extracellular space where it could be taken up by neurons, an event that is believed to contribute to the propagation of tau pathology in the brain. Since the small GTPase Rab7A is involved in the trafficking of endosomes, autophagosomes and lysosomes, and RAB7A gene expression and protein levels are upregulated in AD patients, we tested the hypothesis that Rab7A was involved in Tau secretion. We previously reported that both primary cortical neurons and HeLa cells overexpressing human TAU can release Tau...
February 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28222093/active-zone-proteins-are-transported-via-distinct-mechanisms-regulated-by-par-1-kinase
#6
Kara R Barber, Julia Tanquary, Keegan Bush, Amanda Shaw, Michael Woodson, Michael Sherman, Yogesh P Wairkar
Disruption of synapses underlies a plethora of neurodevelopmental and neurodegenerative disease. Presynaptic specialization called the active zone plays a critical role in the communication with postsynaptic neuron. While the role of many proteins at the active zones in synaptic communication is relatively well studied, very little is known about how these proteins are transported to the synapses. For example, are there distinct mechanisms for the transport of active zone components or are they all transported in the same transport vesicle? Is active zone protein transport regulated? In this report we show that overexpression of Par-1/MARK kinase, a protein whose misregulation has been implicated in Autism spectrum disorders (ASDs) and neurodegenerative disorders, lead to a specific block in the transport of an active zone protein component- Bruchpilot at Drosophila neuromuscular junctions...
February 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28221787/multiple-pesticides-detoxification-function-of-maize-zea-mays-gst34
#7
Dongzhi Li, Li Xu, Sen Pang, Zhiqian Liu, Weisong Zhao, Chengju Wang
ZmGST34 is a maize tau class GST gene and was found to be differently expressed between two maize cultivars differing in tolerance to herbicide metolachlor. To explore the possible role of ZmGST34 in maize development, the expression pattern and substrate specificity of ZmGST34 were characterized by quantitative RT-PCR and heterologous expression system, respectively. The results indicated that the expression level of ZmGST34 was increased approximately 2 to 5-fold per day during the second-leaf stage of maize seedling...
February 21, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28219659/dementia-like-pathology-in-type-2-diabetes-a-novel-microrna-mechanism
#8
Anuradha Kalani, Pankaj Chaturvedi, Claudio Maldonado, Philip Bauer, Irving G Joshua, Suresh C Tyagi, Neetu Tyagi
Although type-2 diabetes (T2D) has been reported to increase the risk of cognitive dysfunction and dementia, the underlying mechanisms remain unclear. Dementia-like pathology is attributed to the accumulation of cellular prion protein (PrP(c)) which plays a role in cognitive dysfunction. However, its involvement and regulation in diabetic dementia-like pathology is not well understood. Using T2D db/db (leptin receptor knockout) mice subjected to object recognition and Y-maze behavioral tests, we determined that short-term memory was compromised and that the mice displayed abrupt spontaneous behaviour compared to db/m control mice...
February 17, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28219440/tau-pet-imaging-present-and-future-directions
#9
REVIEW
Laure Saint-Aubert, Laetitia Lemoine, Konstantinos Chiotis, Antoine Leuzy, Elena Rodriguez-Vieitez, Agneta Nordberg
Abnormal aggregation of tau in the brain is a major contributing factor in various neurodegenerative diseases. The role of tau phosphorylation in the pathophysiology of tauopathies remains unclear. Consequently, it is important to be able to accurately and specifically target tau deposits in vivo in the brains of patients. The advances of molecular imaging in the recent years have now led to the recent development of promising tau-specific tracers for positron emission tomography (PET), such as THK5317, THK5351, AV-1451, and PBB3...
February 20, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28219319/biomarkers-in-alzheimer-s-disease-recent-update
#10
Sushil Sharma, Walter Lipincott
Alzheimer disease (AD) is an age-related neurodegenerative disorder, characterized by loss of memory and cognitive function. It is the common cause of dementia in elderly and is a global health concern as the population of people aged 85 and older, is growing alarmingly. Although pharmacotherapy for the treatment of AD has improved, lot of work remains to treat this devastating disease. AD pathology begins even before the onset of clinical symptoms. Because therapies could be more effective if implemented early in the disease progression, it is highly prudent to discover reliable biomarkers, to detect its exact pathophysiology during pre-symptomatic stage...
February 20, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28218978/biochemical-characterization-of-metabolism-based-atrazine-resistance-in-amaranthus-tuberculatus-and-identification-of-an-expressed-gst-associated-with-resistance
#11
Anton F Evans, Sarah R O'Brien, Rong Ma, Aaron G Hager, Chance W Riggins, Kris N Lambert, Dean E Riechers
Rapid detoxification of atrazine in naturally tolerant crops such as maize (Zea mays) and grain sorghum (Sorghum bicolor) results from glutathione S-transferase (GST) activity. In previous research, two atrazine-resistant waterhemp (Amaranthus tuberculatus) populations from Illinois, U.S.A. (designated ACR and MCR) displayed rapid formation of atrazine-glutathione (GSH) conjugates, implicating elevated rates of metabolism as the resistance mechanism. Our main objective was to utilize protein purification combined with qualitative proteomics to investigate the hypothesis that enhanced atrazine detoxification, catalyzed by distinct GSTs, confers resistance in ACR and MCR...
February 20, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28218850/impact-of-phosphorylation-and-pseudo-phosphorylation-on-the-early-stages-of-aggregation-of-the-microtubule-associated-protein-tau
#12
Dmitriy V Prokopovich, John W Whittaker, Micaiah M Muthee, Azka Ahmed, Luca Larini
The microtubule associated protein tau regulates the stability of microtubules within neurons in the central nervous system. In turn, microtubules are responsible for the remodeling of the cytoskeleton that ultimately leads to the formation or pruning of new connections among neurons. As a consequence, dysfunction of tau is associated with many forms of dementia as well as Alzheimer's disease. In the brain, tau activity is regulated by its phosphorylation state. Phosphorylation is a post-translational modification of proteins that adds a phosphate group to the side chain of an amino acid...
February 20, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28218749/mechanistic-basis-for-the-recognition-of-a-misfolded-protein-by-the-molecular-chaperone-hsp90
#13
Javier Oroz, Jin Hae Kim, Bliss J Chang, Markus Zweckstetter
The critical toxic species in over 40 human diseases are misfolded proteins. Their interaction with molecular chaperones such as Hsp90, which preferentially interacts with metastable proteins, is essential for the blocking of disease progression. Here we used nuclear magnetic resonance (NMR) spectroscopy to determine the three-dimensional structure of the misfolded cytotoxic monomer of the amyloidogenic human protein transthyretin, which is characterized by the release of the C-terminal β-strand and perturbations of the A-B loop...
February 20, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28218731/a-single-use-in-vitro-biosensor-for-the-detection-of-t-tau-protein-a-biomarker-of-neuro-degenerative-disorders-in-pbs-and-human-serum-using-differential-pulse-voltammetry-dpv
#14
Yifan Dai, Alireza Molazemhosseini, Chung Chiun Liu
A single-use, in vitro biosensor for the detection of T-Tau protein in phosphate-buffer saline (PBS) and undiluted human serum was designed, manufactured, and tested. Differential pulse voltammetry (DPV) served as the transduction mechanism. This biosensor consisted of three electrodes: working, counter, and reference electrodes fabricated on a PET sheet. Both working and counter electrodes were thin gold film, 10 nm in thickness. Laser ablation technique was used to define the size and structure of the biosensor...
February 19, 2017: Biosensors
https://www.readbyqxmd.com/read/28217880/follow-up-assessment-of-cognitive-remediation-therapy-in-adolescent-anorexia-nervosa-a-pilot-study
#15
Laura Herbrich, Betteke van Noort, Ernst Pfeiffer, Ulrike Lehmkuhl, Sibylle Winter, Viola Kappel
OBJECTIVE: Cognitive remediation therapy (CRT) is a specialized treatment approach targeting cognitive weaknesses in anorexia nervosa (AN). Regarding follow-up effects of CRT, there are only few studies available; for adolescents, there are no data. METHODS: Forty-eight adolescents with AN were assigned to receive either CRT and treatment as usual (TAU) or TAU alone. Assessments were performed at baseline (n = 48) and compared with assessments at a 6-month follow-up (n = 33)...
March 2017: European Eating Disorders Review: the Journal of the Eating Disorders Association
https://www.readbyqxmd.com/read/28217760/sleep-in-alzheimer-s-disease-beyond-amyloid
#16
Jerrah Holth, Tirth Patel, David M Holtzman
Sleep disorders are prevalent in Alzheimer's disease (AD) and a major cause of institutionalization. Like AD pathology, sleep abnormalities can appear years before cognitive decline and may be predictive of dementia. A bidirectional relationship between sleep and amyloid β (Aβ) has been well established with disturbed sleep and increased wakefulness leading to increased Aβ production and decreased Aβ clearance; whereas Aβ deposition is associated with increased wakefulness and sleep disturbances. Aβ fluctuates with the sleep wake cycle and is higher during wakefulness and lower during sleep...
January 2017: Neurobiology of Sleep and Circadian Rhythms
https://www.readbyqxmd.com/read/28217728/association-between-socioeconomic-and-psychological-experiences-of-parents-with-children-on-leukemia-treatment-in-kenyatta-national-hospital-kenya
#17
Roselyne Anyango Okumu, Margret Muiva, Miriam Wagoro, Fatmah Abdallah, Erick Oweya
OBJECTIVE: The survival rate for children with leukemia has increased dramatically since the late 1990s; treatment effects of the disease can be extremely stressful for families. Research on psychological and socioeconomic effects of leukemia treatment had been conducted in Western countries, but little is known within Africa including Kenya. METHODS: This was a cross-sectional study with a sample of 62 out of 72 parents of children undergoing leukemia treatment at Kenyatta National Hospital...
January 2017: Asia-Pacific Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28217378/role-of-clinical-pathway-in-improving-the-quality-of-care-for-patients-with-faecal-incontinence-a-randomised-trial
#18
Zeiad I Hussain, Michael Lim, Stevan Stojkovic
AIM: To assess the development and implementation of the Integrated Rapid Assessment and Treatment (IRAT) pathway for the management of patients with fecal incontinence and measure its impact on patients' care. METHODS: Patients referred to the colorectal unit in our hospital for the management of faecal incontinence were randomised to either the Standard Care pathway or the newly developed IRAT pathway in this feasibility study. The IRAT pathway is designed to provide a seamless multidisciplinary care to patients with faecal incontinence in a timely fashion...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28217094/in-vivo-evidence-for-therapeutic-properties-of-cannabidiol-cbd-for-alzheimer-s-disease
#19
REVIEW
Georgia Watt, Tim Karl
Alzheimer's disease (AD) is a debilitating neurodegenerative disease that is affecting an increasing number of people. It is characterized by the accumulation of amyloid-β and tau hyperphosphorylation as well as neuroinflammation and oxidative stress. Current AD treatments do not stop or reverse the disease progression, highlighting the need for new, more effective therapeutics. Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has demonstrated neuroprotective, anti-inflammatory and antioxidant properties in vitro...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28215745/astrocyte-transport-of-glutamate-and-neuronal-activity-reciprocally-modulate-tau-pathology-in-drosophila
#20
Jason G Kilian, Heng-Wei Hsu, Kenneth Mata, Fred W Wolf, Masashi Kitazawa
Abnormal buildup of the microtubule associated protein tau is a major pathological hallmark of SAlzheimer's disease (AD)and various tauopathies. The mechanisms by which pathological tau accumulates and spreads throughout the brain remain largely unknown. Previously, we demonstrated that a restoration of the major astrocytic glutamate transporter, GLT1, ameliorated a buildup of tau pathology and rescued cognition in a mouse model of AD. We hypothesized thataberrant extracellular glutamate and abnormal neuronal excitatory activities promoted tau pathology...
February 16, 2017: Neuroscience
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