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Mouse modell for alzheimers disease

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https://www.readbyqxmd.com/read/28320965/deficiency-of-a-sulfotransferase-for-sialic-acid-modified-glycans-mitigates-alzheimer-s-pathology
#1
Zui Zhang, Yoshiko Takeda-Uchimura, Tahmina Foyez, Shiori Ohtake-Niimi, Narentuya, Hiroyasu Akatsu, Kazuchika Nishitsuji, Makoto Michikawa, Tony Wyss-Coray, Kenji Kadomatsu, Kenji Uchimura
We previously showed that microglial keratan sulfate (KS) was induced in amyotrophic lateral sclerosis. However, the functional roles of the glycan and its synthetic enzyme in neurodegenerative diseases, such as Alzheimer's disease (AD), a progressive disorder, are unclear. In our study, KS modified with sialic acids having a molecular mass of 125-220 kDa and the carbohydrate sulfotransferase GlcNAc6ST1 were up-regulated in the brains of two transgenic mouse models (J20 and Tg2576) and the brains of patients with AD...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320590/multitep-platform-based-dna-epitope-vaccine-targeting-n-terminus-of-tau-induces-strong-immune-responses-and-reduces-tau-pathology-in-thy-tau22-mice
#2
Hayk Davtyan, Wesley W Chen, Karen Zagorski, Joy Davis, Irina Petrushina, Konstantin Kazarian, David H Cribbs, Michael G Agadjanyan, Mathew Blurton-Jones, Anahit Ghochikyan
BACKGROUND: By the time clinical symptoms of Alzheimer's disease (AD) manifest in patients there is already substantial tau pathology in the brain. Recent evidence also suggests that tau pathology can become self-propagating, further accelerating disease progression. Over the last decade several groups have tested the efficacy of protein-based anti-tau immunotherapeutics in various animal models of tauopathy. Here we report on the immunological and therapeutic potency of the first anti-tau DNA vaccine based on the MultiTEP platform, AV-1980D, in THY-Tau22 transgenic mice...
March 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28318232/histology-compatible-maldi-mass-spectrometry-based-imaging-of-neuronal-lipids-for-subsequent-immunofluorescent-staining
#3
Ibrahim Kaya, Wojciech Michno, Dimitri Brinet, Yasmine Iacone, Giulia Zanni, Kaj Blennow, Henrik Zetterberg, Jörg Hanrieder
Matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables acquisition of spatial distribution maps for molecular species in situ. This can provide comprehensive insights on the pathophysiology of different diseases. However, current sample preparation and MALDI-IMS acquisition methods have limitations in preserving molecular and histological tissue morphology, resulting in interfered correspondence of MALDI-IMS data with subsequently acquired immunofluorescent staining results...
March 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28317486/abnormal-clock-gene-expression-and-locomotor-activity-rhythms-in-two-month-old-female-appswe-ps1de9-mice
#4
Olaide Oyegbami, Hilary M Collins, Marie C Pardon, Fran Jp Ebling, David M Heery, Paula M Moran
In addition to cognitive decline, Alzheimer's disease (AD) is also characterized by agitation and disruptions in activity and sleep. These symptoms typically occur in the evening or at night and have been referred to as 'sundowning'. These symptoms are especially difficult for carers and there are no specific drug treatments. There is increasing evidence that these symptoms reflect an underlying pathology of circadian rhythm generation and transmission. We investigated whether a transgenic mouse model relevant to AD (APPswe/PS1dE9) exhibits circadian alterations in locomotor activity and expression of clock genes involved in the regulation of the circadian cycle...
March 17, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28315264/the-evolution-of-the-sigma-2-%C3%AF-2-receptor-from-obscure-binding-site-to-bona-fide-therapeutic-target
#5
Chenbo Zeng, Robert H Mach
The sigma-2 (σ2) receptor represents one of the most poorly understood proteins in cell biology. Although this receptor was identified through in vitro binding studies over 25 years ago, the molecular identity of this protein is currently not unambiguously known, and the results from recent attempts to identify the σ2 receptor through protein purification and mass spectral analysis have been the subject of debate in the literature. However, there is overwhelming data demonstrating that the σ2 receptor is an important biomarker of tumor cell proliferation ...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28304309/mouse-models-of-alzheimer-s-disease
#6
Gisela Esquerda-Canals, Laia Montoliu-Gaya, Jofre Güell-Bosch, Sandra Villegas
Alzheimer's disease (AD) is a neurodegenerative disorder that nowadays affects more than 40 million people worldwide and it is predicted to exponentially increase in the coming decades. Because no curative treatment exists, research on the pathophysiology of the disease, as well as the testing of new drugs, are mandatory. For these purposes, animal models constitute a valuable, although perfectible tool. This review takes a tour through several aspects of mouse models of AD, such as the generation of transgenic models, the relevance of the promoter driving the expression of the transgenes, and the concrete transgenes used to simulate AD pathophysiology...
March 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28303140/netosis-in-alzheimer-s-disease
#7
REVIEW
Enrica Caterina Pietronigro, Vittorina Della Bianca, Elena Zenaro, Gabriela Constantin
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive deterioration of cognitive functions. Its neuropathological features include amyloid-β (Aβ) accumulation, the formation of neurofibrillary tangles, and the loss of neurons and synapses. Neuroinflammation is a well-established feature of AD pathogenesis, and a better understanding of its mechanisms could facilitate the development of new therapeutic approaches. Recent studies in transgenic mouse models of AD have shown that neutrophils adhere to blood vessels and migrate inside the parenchyma...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28300838/membrane-association-and-release-of-wild-type-and-pathological-tau-from-organotypic-brain-slice-cultures
#8
Cara L Croft, Matthew A Wade, Ksenia Kurbatskaya, Pavlina Mastrandreas, Martina M Hughes, Emma C Phillips, Amy M Pooler, Michael S Perkinton, Diane P Hanger, Wendy Noble
The spatiotemporal transmission of pathological tau in the brain is characteristic of Alzheimer's disease. Release of both soluble and abnormal tau species from healthy neurons is increased upon stimulation of neuronal activity. It is not yet understood whether the mechanisms controlling soluble tau release from healthy neurons is the same as those involved in the spread of pathological tau species. To begin to understand these events, we have studied tau distribution and release using organotypic brain slice cultures...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28299805/novel-ketone-body-therapy-for-managing-alzheimer-s-disease-an-editorial-highlight-for-effects-of-a-dietary-ketone-ester-on-hippocampal-glycolytic-and-tricarboxylic-acid-cycle-intermediates-and-amino-acids-in-a-3xtgad-mouse-model-of-alzheimer-s-disease
#9
EDITORIAL
Michelle A Puchowicz, Thomas N Seyfried
Read the highlighted article 'Effects of a dietary ketone ester on hippocampal glycolytic and tricarboxylic acid cycle intermediates and amino acids in a 3xTgAD mouse model of Alzheimer's disease' on doi: 10.1111/jnc.13958.
March 15, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28298426/modeling-alzheimer-s-disease-in-mice-with-human-neurons
#10
Gaia Novarino
Human neurons transplanted into a mouse model for Alzheimer's disease show human-specific vulnerability to β-amyloid plaques and may help to identify new therapeutic targets.
March 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28295437/a-novel-assay-to-determine-acetylcholinesterase-activity-the-application-potential-for-screening-of-drugs-against-alzheimer-s-disease
#11
Liang Peng, Zhengxing Rong, Hao Wang, Biyun Shao, Lei Kang, Hong Qi, Hongzhuan Chen
Acetycholinesterase (AChE) that regulates hydrolysis of acetylcholine (ACh) in the brain, is an important target for treatment of Alzheimer's disease (AD) featured by ACh deficiency. However, the methods to precisely determine AChE activity are still under development. Here, we created a new method to exploit acetylcholine-d4 (ACh-d4 ) as a surrogate substrate of ACh and measure product choline-d4 (Ch-d4 ) via liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay detected activity of AChE present in the normal mouse brain, which is consistent with the standard Ellman assay that determines products spectrophotometrically...
March 10, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28289387/analyses-of-mrna-profiling-through-rna-sequencing-on-a-samp8-mouse-model-in-response-to-ginsenoside-rg1-and-rb1-treatment
#12
Shuai Zhang, Dina Zhu, Hong Li, Haijing Zhang, Chengqiang Feng, Wensheng Zhang
Ginsenoside Rg1 and Rb1 are the major ingredients in two medicines called QiShengLi (Z20027165) and QiShengJing (Z20027164) approved by China. These ingredients are believed to mitigate forgetfulness. Numerous studies have confirmed that GRg1 and GRb1 offer protection against Alzheimer's disease (AD), and our morris water maze (MWM) experiment also indicated that GRg1 and GRb1 may attenuate memory deficits in the 7-month-old SAMP8 mice; however, comprehensive understanding of their roles in AD remains limited...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28287086/pre-plaque-conformational-changes-in-alzheimer-s-disease-linked-a%C3%AE-and-app
#13
O Klementieva, K Willén, I Martinsson, B Israelsson, A Engdahl, J Cladera, P Uvdal, G K Gouras
Reducing levels of the aggregation-prone Aβ peptide that accumulates in the brain with Alzheimer's disease (AD) has been a major target of experimental therapies. An alternative approach may be to stabilize the physiological conformation of Aβ. To date, the physiological state of Aβ in brain remains unclear, since the available methods used to process brain tissue for determination of Aβ aggregate conformation can in themselves alter the structure and/or composition of the aggregates. Here, using synchrotron-based Fourier transform infrared micro-spectroscopy, non-denaturing gel electrophoresis and conformational specific antibodies we show that the physiological conformations of Aβ and amyloid precursor protein (APP) in brain of transgenic mouse models of AD are altered before formation of amyloid plaques...
March 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28286181/amplifying-mitochondrial-function-rescues-adult-neurogenesis-in-a-mouse-model-of-alzheimer-s-disease
#14
Kevin Richetin, Manon Moulis, Aurélie Millet, Macarena S Arràzola, Trinovita Andraini, Jennifer Hua, Noélie Davezac, Laurent Roybon, Pascale Belenguer, Marie-Christine Miquel, Claire Rampon
Adult hippocampal neurogenesis is strongly impaired in Alzheimer's disease (AD). In several mouse models of AD, it was shown that adult-born neurons exhibit reduced survival and altered synaptic integration due to a severe lack of dendritic spines. In the present work, using the APPxPS1 mouse model of AD, we reveal that this reduced number of spines is concomitant of a marked deficit in their neuronal mitochondrial content. Remarkably, we show that targeting the overexpression of the pro-neural transcription factor Neurod1 into APPxPS1 adult-born neurons restores not only their dendritic spine density, but also their mitochondrial content and the proportion of spines associated with mitochondria...
March 10, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28284842/ageing-and-chronic-intermittent-hypoxia-mimicking-sleep-apnea-do-not-modify-local-brain-tissue-stiffness-in-healthy-mice
#15
Ignasi Jorba, Maria José Menal, Marta Torres, David Gozal, Gerard Piñol-Ripoll, Anna Colell, Josep M Montserrat, Daniel Navajas, Ramon Farré, Isaac Almendros
Recent evidence suggests that obstructive sleep apnea (OSA) may increase the risk of Alzheimer´s disease (AD), with the latter promoting alterations in brain tissue stiffness, a feature of ageing. Here, we assessed the effects of age and intermittent hypoxia (IH) on brain tissue stiffness in a mouse model of OSA. Two-month-old and 18-month-old mice (N=10 each) were subjected to IH (20% O2 40s - 6% O2 20s) for 8 weeks (6h/day). Corresponding control groups for each age were kept under normoxic conditions in room air (RA)...
March 6, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28284226/enhanced-susceptibility-of-triple-transgenic-alzheimer-s-disease-3xtg-ad-mice-to-acute-infection
#16
Rebecca Montacute, Kerry Foley, Ruth Forman, Kathryn Jane Else, Sheena Margaret Cruickshank, Stuart McRae Allan
BACKGROUND: Infection is a recognised risk factor for Alzheimer's disease (AD) and can worsen symptoms in established disease. AD patients have higher rates of infection and are more likely to require hospital admissions due to infections than individuals without dementia. Infections have also been found to increase the risk of those over 84 years of age being diagnosed with dementia. However, few studies have investigated immune responses to infection in AD. METHODS: Here, we investigated the immune responses of the triple transgenic Alzheimer's disease (3xTg-AD) mouse model of AD to infection with the parasites Toxoplasma gondii and Trichuris muris...
March 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28279360/testing-the-amyloid-hypothesis-with-a-humanized-ad-mouse-model
#17
Michelle K Cahill, Eric J Huang
In this issue of Neuron, Espuny-Camacho et al. (2017) generate a humanized Alzheimer's disease (AD) model that reveals species-specific vulnerability of human neurons to AD pathology. This model provides key insights for disease mechanism and therapeutic discovery for AD.
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28277939/potassium-channel-expression-and-function-in-microglia-plasticity-and-possible-species-variations
#18
Hai M Nguyen, Linda V Blomster, Palle Christophersen, Heike Wulff
Potassium channels play important roles in microglia functions and thus constitute potential targets for the treatment of neurodegenerative diseases like Alzheimer's, Parkinson's and stroke. However, uncertainty still prevails as to which potassium channels are expressed and at what levels in different species, how the expression pattern changes upon activation with M1 or M2 polarizing stimuli compared to more complex exposure paradigms, and - most importantly - how these findings relate to the in vivo situation...
March 1, 2017: Channels
https://www.readbyqxmd.com/read/28275722/differential-contribution-of-app-metabolites-to-early-cognitive-deficits-in-a-tgcrnd8-mouse-model-of-alzheimer-s-disease
#19
Valentine Hamm, Céline Héraud, Jean-Bastien Bott, Karine Herbeaux, Carole Strittmatter, Chantal Mathis, Romain Goutagny
Alzheimer's disease (AD) is a neurodegenerative pathology commonly characterized by a progressive and irreversible deterioration of cognitive functions, especially memory. Although the etiology of AD remains unknown, a consensus has emerged on the amyloid hypothesis, which posits that increased production of soluble amyloid β (Aβ) peptide induces neuronal network dysfunctions and cognitive deficits. However, the relative failures of Aβ-centric therapeutics suggest that the amyloid hypothesis is incomplete and/or that the treatments were given too late in the course of AD, when neuronal damages were already too extensive...
February 2017: Science Advances
https://www.readbyqxmd.com/read/28275161/astrocytic-lrp1-mediates-brain-a%C3%AE-clearance-and-impacts-amyloid-deposition
#20
Chia-Chen Liu, Jin Hu, Na Zhao, Jian Wang, Wang Na, John R Cirrito, Takahisa Kanekiyo, David M Holtzman, Guojun Bu
Accumulation and deposition of amyloid-β (Aβ) in the brain represents an early and perhaps necessary step in the pathogenesis of Alzheimer's disease (AD). Aβ accumulation leads to the formation of Aβ aggregates which may directly and indirectly lead to eventual neurodegeneration. While Aβ production is accelerated in many familial forms of early-onset AD, increasing evidence indicates that impaired clearance of Aβ is more evident in late-onset AD. To uncover the mechanisms underlying impaired Aβ clearance in AD, we examined the role of low-density lipoprotein receptor-related protein 1 (LRP1) in astrocytes...
March 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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