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Mouse modell for alzheimers disease

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https://www.readbyqxmd.com/read/29333090/gene-and-protein-expression-profiles-in-a-mouse-model-of-collagen-induced-arthritis
#1
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/29332049/free-heme-and-amyloid-%C3%AE-a-fatal-liaison-in-alzheimer-s-disease
#2
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/29332044/does-the-genetic-feature-of-the-chinese-tree-shrew-tupaia-belangeri-chinensis-support-its-potential-as-a-viable-model-for-alzheimer-s-disease-research
#3
Yu Fan, Rongcan Luo, Ling-Yan Su, Qun Xiang, Dandan Yu, Ling Xu, Jia-Qi Chen, Rui Bi, Dong-Dong Wu, Ping Zheng, Yong-Gang Yao
Alzheimer's disease (AD) is a neurodegenerative disease with increasing incidence across the world and no cure at the present time. An ideal animal model would facilitate the understanding of the pathogenesis of AD and discovery of potential therapeutic targets. The Chinese tree shrew (Tupaia belangeri chinensis) has a closer genetic affinity to primates relative to rodents, and can attain ages of 8 years or older, which represents another advantage for the study of neurodegenerative diseases such as AD compared to primates...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332042/protective-effects-of-indian-spice-curcumin-against-amyloid-%C3%AE-in-alzheimer-s-disease
#4
P Hemachandra Reddy, Maria Manczak, Xiangling Yin, Mary Catherine Grady, Andrew Mitchell, Sahil Tonk, Chandra Sekhar Kuruva, Jasvinder Singh Bhatti, Ramesh Kandimalla, Murali Vijayan, Subodh Kumar, Rui Wang, Jangampalli Adi Pradeepkiran, Gilbert Ogunmokun, Kavya Thamarai, Kandi Quesada, Annette Boles, Arubala P Reddy
The purpose of our article is to assess the current understanding of Indian spice, curcumin, against amyloid-β (Aβ)-induced toxicity in Alzheimer's disease (AD) pathogenesis. Natural products, such as ginger, curcumin, and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes, and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332035/an-aspartyl-cathepsin-targeted-pet-agent-application-in-an-alzheimer-s-disease-mouse-model
#5
Jonatan A Snir, Mojmir Suchy, Geron A Bindseil, Michael Kovacs, Blaine A Chronik, Robert H E Hudson, Stephen H Pasternak, Robert Bartha
BACKGROUND: Early detection of Alzheimer's disease (AD) pathology is a serious challenge for both diagnosis and clinical trials. The aspartyl protease, Cathepsin D (CatD), is overexpressed in AD and could be a biomarker of disease. We have previously designed a unique contrast agent (CA) for dual-optical and magnetic resonance imaging of the activity of the CatD class of enzymes. OBJECTIVE: To compare the uptake and retention of a novel, more sensitive, and clinically-translatable 68Ga PET tracer targeting CatD activity in 5XFAD mice and non-Tg littermates...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29329433/rage-mediates-a%C3%AE-accumulation-in-a-mouse-model-of-alzheimer-s-disease-via-modulation-of-%C3%AE-and-%C3%AE-secretase-activity
#6
Fang Fang, Qing Yu, Ottavio Arancio, Doris Chen, Smruti S Gore, Shi Fang Yan, Shirley ShiDu Yan
Receptor for Advanced Glycation End products (RAGE) has been implicated in amyloid β-peptide (Aβ)-induced perturbation relevant to the pathogenesis of Alzheimer's disease (AD). However, whether and how RAGE regulates Aβ metabolism remains largely unknown. Aβ formation arises from aberrant cleavage of amyloid precursor protein (APP) by β- and γ-secretase. To investigate whether RAGE modulates β- and γ-secretase activity potentiating Aβ formation, we generated mAPP mice with genetic deletion of RAGE (mAPP/RO)...
January 10, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29328926/dna-damage-associated-oligodendrocyte-degeneration-precedes-amyloid-pathology-and-contributes-to-alzheimer-s-and-dementia
#7
Kai-Hei Tse, Aifang Cheng, Fulin Ma, Karl Herrup
INTRODUCTION: In looking for novel non-amyloid-based etiologies for Alzheimer's disease, we explore the hypothesis that age-related myelin loss is an attractive explanation for age-associated cognitive decline and dementia. METHODS: We performed a meta-analysis of data in the National Alzheimer's Coordinating Center database accompanied by quantitative histopathology of myelin and oligodendrocytes (OLs) in frontal cortices of 24 clinically characterized individuals...
January 9, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29325995/acetylshikonin-from-zicao-attenuates-cognitive-impairment-and-hippocampus-senescence-in-d-galactose-induced-aging-mouse-model-via-upregulating-the-expression-of-sirt1
#8
Qisen Li, Jiacheng Zeng, Meiling Su, Yu He, Banghao Zhu
Zicao acts as a pleiotropic medicine in various diseases due to its particular pharmacological properties, including anti-inflammatory, anti-tumor, anti-oxidative, and wound healing effects. However, few studies have focused on the function in neurodegenerative diseases of Zicao. In this study, we investigated the neuroprotective effect of Acetylshikonin (AS) from Zicao on the hippocampus of the D-galactose (D-gal)-induced sub-acute aging mouse model of Alzheimer's disease (AD). The aging model was established in male Kunming mice by subcutaneous injection of D-gal (150 mg/kg/d) for 60 days, and the mice were given AS (270, 540 and 1080 mg/kg/d) or distilled water intragastrically for 30 days after 30 days of D-gal injection...
January 8, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29325805/reduced-plaque-size-and-inflammation-in-the-app23-mouse-model-for-alzheimer-s-disease-after-chronic-application-of-polymeric-nanoparticles-for-cns-targeted-zinc-delivery
#9
Antonietta Vilella, Daniela Belletti, Ann Katrin Sauer, Simone Hagmeyer, Tasnuva Sarowar, Martina Masoni, Natalia Stasiak, John J E Mulvihill, Barbara Ruozi, Flavio Forni, Maria Angela Vandelli, Giovanni Tosi, Michele Zoli, Andreas M Grabrucker
A local dyshomeostasis of zinc ions in the vicinity of amyloid aggregates has been proposed in Alzheimer's disease (AD) due to the sequestration of zinc in senile plaques. While an increase in zinc levels may promote the aggregation of amyloid beta (Aβ), increased brain zinc might also be beneficial rescuing some pathological alterations caused by local zinc deficiency. For example, increased Aβ degradation by metalloproteinases, and a reduction in inflammation can be hypothesized. In addition, zinc may allow a stabilization of the number of synapses in AD brains...
December 27, 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29322650/molecular-characterization-of-the-%C3%AE-amyloid-4-10-epitope-of-plaque-specific-a%C3%AE-antibodies-by-affinity-mass-spectrometry-using-alanine-site-mutation
#10
Raluca Ștefănescu, Loredana Lupu, Marilena Manea, Roxana E Iacob, Michael Przybylski
Alzheimer disease is a neurodegenerative disease affecting an increasing number of patients worldwide. Current therapeutic strategies are directed to molecules capable to block the aggregation of the β-amyloid(1-42) (Aβ) peptide and its shorter naturally occurring peptide fragments into toxic oligomers and amyloid fibrils. Aβ-specific antibodies have been recently developed as powerful antiaggregation tools. The identification and functional characterization of the epitope structures of Aβ antibodies contributes to the elucidation of their mechanism of action in the human organism...
January 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29321508/thrombospondin-1-secreted-by-human-umbilical-cord-blood-derived-mesenchymal-stem-cells-rescues-neurons-from-synaptic-dysfunction-in-alzheimer-s-disease-model
#11
Dong Hyun Kim, Hoon Lim, Dahm Lee, Soo Jin Choi, Wonil Oh, Yoon Sun Yang, Jeong Su Oh, Hyun Ho Hwang, Hong Bae Jeon
Alzheimer's disease (AD) is an incurable neurodegenerative disease characterised clinically by learning and memory impairments. Amyloid beta (Aβ) peptide-induced synaptic dysfunction is a pathological process associated with early-stage AD. Here, we show that paracrine action of human umbilical cord blood-derived-mesenchymal stem cells (hUCB-MSCs) protects the hippocampus from synaptic-density loss in in vitro and in vivo AD models. To identify paracrine factors underlying this rescue effect, we analysed hUCB-MSCs' secretome co-cultured with Aβ42-treated mouse hippocampal neurons...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316249/the-mitochondrial-atp-synthase-is-a-shared-drug-target-for-aging-and-dementia
#12
Joshua Goldberg, Antonio Currais, Marguerite Prior, Wolfgang Fischer, Chandramouli Chiruta, Eric Ratliff, Daniel Daugherty, Richard Dargusch, Kim Finley, Pau B Esparza-Moltó, José M Cuezva, Pamela Maher, Michael Petrascheck, David Schubert
Aging is a major driving force underlying dementia, such as that caused by Alzheimer's disease (AD). While the idea of targeting aging as a therapeutic strategy is not new, it remains unclear how closely aging and age-associated diseases are coupled at the molecular level. Here, we discover a novel molecular link between aging and dementia through the identification of the molecular target for the AD drug candidate J147. J147 was developed using a series of phenotypic screening assays mimicking disease toxicities associated with the aging brain...
January 7, 2018: Aging Cell
https://www.readbyqxmd.com/read/29314494/dysregulation-of-rab5-mediated-endocytic-pathways-in-alzheimer-s-disease
#13
REVIEW
Wei Xu, Fang Fang, Jianqing Ding, Chengbiao Wu
Increasing evidence has pointed to that dysregulation of the endo-lysosomal system is an early cellular phenotype of pathogenesis for Alzheimer's disease (AD). Rab5, a small GTPase, plays a critical role in mediating these processes. Abnormal overactivation of Rab5 has been observed in post-mortem brain samples of Alzheimer's patients as well as brain samples of mouse models of AD. Recent genome-wide association studies of Alzheimer's disease have identified RIN3 (Ras and Rab Interactor 3) as a novel risk factor for the disease...
January 3, 2018: Traffic
https://www.readbyqxmd.com/read/29309769/sloh-a-carbazole-based-fluorophore-mitigates-neuropathology-and-behavioral-impairment-in-the-triple-transgenic-mouse-model-of-alzheimer-s-disease
#14
Xiaoli Wu, Jayasankar Kosaraju, Wei Zhou, Kin Yip Tam
Alzheimer's disease (AD) is a progressive neurodegenerative dysfunction characterized by memory impairment and brings a heavy burden to old people both in developing and developed countries. Amyloid hypothesis reveals that aggregation and deposition of amyloid plaques are the cause of AD neurodegeneration. SLOH, a carbazole-based fluorophore, is reported to inhibit amyloid beta (Aβ) aggregation in vitro. In the current study, we intended to evaluate the protective effect of SLOH in a triple transgenic AD mouse model (3xTg-AD)...
January 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29303606/potential-neuroprotective-and-anti-apoptotic-properties-of-a-long-lasting-stable-analog-of-ghrelin-an-in-vitro-study-using-sh-sy5y-cells
#15
A Popelová, A Kákonová, L Hrubá, J Kuneš, L Maletínská, B Železná
Neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are increasing in prevalence. Currently, there are no effective and specific treatments for these disorders. Recently, positive effects of the orexigenic hormone ghrelin on memory and learning were demonstrated in mouse models of AD and PD. In this study, we tested the potential neuroprotective properties of a stable and long-lasting ghrelin analog, Dpr(3)ghrelin (Dpr(3)ghr), in SH-SY5Y neuroblastoma cells stressed with 1...
January 5, 2018: Physiological Research
https://www.readbyqxmd.com/read/29302204/metagenome-analysis-of-bodily-microbiota-in-a-mouse-model-of-alzheimer-disease-using-bacteria-derived-membrane-vesicles-in-blood
#16
Jin-Young Park, Juli Choi, Yunjin Lee, Jung-Eun Lee, Eun-Hwa Lee, Hye-Jin Kwon, Jinho Yang, Bo-Ri Jeong, Yoon-Keun Kim, Pyung-Lim Han
Emerging evidence has suggested that the gut microbiota contribute to brain dysfunction, including pathological symptoms of Alzheimer disease (AD). Microbiota secrete membrane vesicles, also called extracellular vesicles (EVs), which contain bacterial genomic DNA fragments and other molecules and are distributed throughout the host body, including blood. In the present study, we investigated whether bacteria-derived EVs in blood are useful for metagenome analysis in an AD mouse model. Sequence readings of variable regions of 16S rRNA genes prepared from blood EVs in Tg-APP/PS1 mice allowed us to identify over 3,200 operational taxonomic units corresponding to gut microbiota reported in previous studies...
December 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/29301548/inhibition-of-cyclin-dependent-kinase-5-affects-early-neuroinflammatory-signalling-in-murine-model-of-amyloid-beta-toxicity
#17
Anna Wilkaniec, Magdalena Gąssowska-Dobrowolska, Marcin Strawski, Agata Adamczyk, Grzegorz A Czapski
BACKGROUND: Cyclin-dependent kinase 5 (Cdk5) belongs to the family of proline-directed serine/threonine kinases and plays a critical role in neuronal differentiation, migration, synaptogenesis, plasticity, neurotransmission and apoptosis. The deregulation of Cdk5 activity was observed in post mortem analysis of brain tissue of Alzheimer's disease (AD) patients, suggesting the involvement of Cdk5 in the pathomechanism of this neurodegenerative disease. However, our recent study demonstrated the important function of Cdk5 in regulating inflammatory reaction...
January 4, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29298895/endoplasmic-reticulum-stress-responses-in-mouse-models-of-alzheimer-disease-overexpression-paradigm-versus-knock-in-paradigm
#18
Shoko Hashimoto, Ayano Ishii, Naoko Kamano, Naoto Watamura, Takashi Saito, Toshio Oshima, Makoto Yokosuka, Takaomi C Saido
Endoplasmic reticulum (ER) stress is believed to play an important role in the etiology of Alzheimer disease (AD). The accumulation of misfolded proteins and perturbation of intracellular calcium homeostasis are thought to underlie the induction of ER stress, resulting in neuronal dysfunction and cell death. Several reports have shown an increased ER stress response in amyloid precursor protein (APP) and presenilin1 (PS1) double transgenic (Tg) AD mouse models. However, it remains unclear whether the ER stress observed in these mouse models is actually caused by AD pathology...
January 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29298417/brain-shuttle-antibody-for-alzheimer-s-disease-with-attenuated-peripheral-effector-function-due-to-an-inverted-binding-mode
#19
Felix Weber, Bernd Bohrmann, Jens Niewoehner, Jens A A Fischer, Petra Rueger, Georg Tiefenthaler, Joerg Moelleken, Alexander Bujotzek, Kevin Brady, Thomas Singer, Martin Ebeling, Antonio Iglesias, Per-Ola Freskgård
Receptors show promise for the transport of monoclonal antibodies (mAbs) across the blood-brain barrier. However, safety liabilities associated with peripheral receptor binding and Fc effector function have been reported. We present the Brain Shuttle-mAb (BS-mAb) technology, and we investigate the role of Fc effector function in vitro and in an Fcγ receptor (FcγR)-humanized mouse model. Strong first infusion reactions (FIRs) were observed for a conventional mAb against transferrin receptor (TfR) with a wild-type immunoglobulin G1 (IgG1) Fc...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29298040/functionalization-and-characterization-of-magnetic-nanoparticles-for-the-detection-of-ferritin-accumulation-in-alzheimer-s-disease
#20
Tamara Fernández, Alberto Martínez-Serrano, Lorena Cussó, Manuel Desco, Milagros Ramos-Gómez
Early diagnosis in Alzheimer's disease (AD), prior to the appearance of marked clinical symptoms, is critical to prevent irreversible neuronal damage and neural malfunction that leads to dementia and death. Therefore, there is an urgent need to generate new contrast agents which reveal by a non-invasive method the presence of some of the pathological signs of AD. In the present study we demonstrate for the first time a new nanoconjugate composed of magnetic nanoparticles bound to an anti-ferritin antibody, which has been developed based on the existence of iron deposits and high levels of the ferritin protein present in areas with a high accumulation of amyloid plaques (particularly the subiculum in the hippocampal area) in the brain of a transgenic mouse model with five familial AD mutations...
January 3, 2018: ACS Chemical Neuroscience
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