scholarly journals A novel BACE inhibitor NB-360 shows a superior pharmacological profile and robust reduction of amyloid-β and neuroinflammation in APP transgenic mice

2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Ulf Neumann ◽  
Heinrich Rueeger ◽  
Rainer Machauer ◽  
Siem Jacob Veenstra ◽  
Rainer M. Lueoend ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Amyloid Β ◽  
Pharmacological Profile ◽  
Bace Inhibitor

Berberine Alleviates Amyloid-beta Pathogenesis Via Activating LKB1/AMPK Signaling in the Brain of APP/PS1 Transgenic Mice

2019 ◽  
Vol 19 (5) ◽  
pp. 342-348 ◽  
Author(s):  
Zhi-You Cai ◽  
Chuan-Ling Wang ◽  
Tao-Tao Lu ◽  
Wen-Ming Yang
Keyword(s):  
Transgenic Mice ◽  
Western Blotting ◽  
Amyloid Β ◽  
Adenosine Monophosphate ◽  
Camp Response Element Binding ◽  
Enzyme Linked Immunosorbent Assay ◽  
Synaptic Density ◽  
Ampk Signaling ◽  
The Brain ◽  
Post Synaptic Density

Background:Liver kinase B1 (LKB1)/5’-adenosine monophosphate-activated protein kinase (AMPK) signaling, a metabolic checkpoint, plays a neuro-protective role in the pathogenesis of Alzheimer’s disease (AD). Amyloid-β (Aβ) acts as a classical biomarker of AD. The aim of the present study was to explore whether berberine (BBR) activates LKB1/AMPK signaling and ameliorates Aβ pathology.Methods:The Aβ levels were detected using enzyme-linked immunosorbent assay and immunohistochemistry. The following biomarkers were measured by Western blotting: phosphorylated (p-) LKB1 (Ser334 and Thr189), p-AMPK (AMPKα and AMPKβ1), synaptophysin, post-synaptic density protein 95 and p-cAMP-response element binding protein (p-CREB). The glial fibrillary acidic protein (GFAP) was determined using Western blotting and immunohistochemistry.Results:BBR inhibited Aβ expression in the brain of APP/PS1 mice. There was a strong up-regulation of both p-LKB1 (Ser334 and Thr189) and p-AMPK (AMPKα and AMPKβ1) in the brains of APP/PS1 transgenic mice after BBR-treatment (P<0.01). BBR promoted the expression of synaptophysin, post-synaptic density protein 95 and p-CREB(Ser133) in the AD brain, compared with the model mice.Conclusion:BBR alleviates Aβ pathogenesis and rescues synapse damage via activating LKB1/AMPK signaling in the brain of APP/PS1 transgenic mice.

scholarly journals Chronic cerebral hypoperfusion accelerates amyloid β deposition in APPSwInd transgenic mice

2009 ◽  
Vol 1294 ◽  
pp. 202-210 ◽  
Author(s):  
Hiroshi Kitaguchi ◽  
Hidekazu Tomimoto ◽  
Masafumi Ihara ◽  
Masunari Shibata ◽  
Kengo Uemura ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Amyloid Β ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion

scholarly journals Induction of Tau Pathology by Intracerebral Infusion of Amyloid-β-Containing Brain Extract and by Amyloid-β Deposition in APP × Tau Transgenic Mice

2007 ◽  
Vol 171 (6) ◽  
pp. 2012-2020 ◽  
Author(s):  
Tristan Bolmont ◽  
Florence Clavaguera ◽  
Melanie Meyer-Luehmann ◽  
Martin C. Herzig ◽  
Rebecca Radde ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Amyloid Β ◽  
Brain Extract ◽  
Tau Pathology ◽  
Intracerebral Infusion

scholarly journals In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid β-peptide of APP

2010 ◽  
Vol 48 (1) ◽  
pp. 136-144 ◽  
Author(s):  
D. Allan Butterfield ◽  
Veronica Galvan ◽  
Miranda Bader Lange ◽  
Huidong Tang ◽  
Renã A. Sowell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Transgenic Mice ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Methionine 35

scholarly journals Neuroprotective Effects of Asparagus officinalis Stem Extract in Transgenic Mice Overexpressing Amyloid Precursor Protein

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhanglong Peng ◽  
Supinder Bedi ◽  
Vivek Mann ◽  
Alamelu Sundaresan ◽  
Kohei Homma ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Amyloid Precursor Protein ◽  
Caspase 3 ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Tau Proteins ◽  
Asparagus Officinalis ◽  
Mouse Strains ◽  
Neuroprotective Effects ◽  
Shock Proteins

To mimic Alzheimer’s disease, transgenic mice overexpressing the amyloid precursor protein (APP) were used in this study. We hypothesize that the neuroprotective effects of ETAS®50, a standardized extract of Asparagus officinalis stem produced by Amino Up Co., Ltd. (Sapporo, Japan), are linked to the inhibition of the apoptosis cascade through an enhancement of the stress-response proteins: heat shock proteins (HSPs). APP-overexpressing mice (double-transgenic APP and PS1 mouse strains with a 129s6 background), ages 6-8 weeks old, and weighing 20-24 grams were successfully bred in our laboratory. The animals were divided into 5 groups. APP-overexpressing mice and wild-type (WT) mice were pretreated with ETAS®50 powder (50% elemental ETAS and 50% destrin) at 200 mg/kg and 1000 mg/kg body weight. Saline, the vehicle for ETAS®50, was administered in APP-overexpressing mice and WT mice. ETAS®50 and saline were administered by gavage daily for 1 month. Cognitive assessments, using the Morris Water Maze, demonstrated that memory was recovered following ETAS®50 treatment as compared to nontreated APP mice. At euthanization, the brain was removed and HSPs, amyloid β, tau proteins, and caspase-3 were evaluated through immunofluorescence staining with the appropriate antibodies. Our data indicate that APP mice have cognitive impairment along with elevated amyloid β, tau proteins, and caspase-3. ETAS®50 restored cognitive function in these transgenic mice, increased both HSP70 and HSP27, and attenuated pathogenic level of amyloid β, tau proteins, and caspsase-3 leading to neuroprotection. Our results were confirmed with a significant increase in HSP70 gene expression in the hippocampus.

O3-01-01: Amyloid-β protofibrils are linked to cognitive impairment in Alzheimer's disease transgenic mice

2008 ◽  
Vol 4 ◽  
pp. T157-T157
Author(s):  
Anna Lord ◽  
Hillevi Englund ◽  
Fredrik Clausen ◽  
Lars Hillered ◽  
Frida Ekholm Pettersson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Transgenic Mice ◽  
Amyloid Β

scholarly journals Cerebral Microvascular Rather than Parenchymal Amyloid-β Protein Pathology Promotes Early Cognitive Impairment in Transgenic Mice

2013 ◽  
Vol 38 (3) ◽  
pp. 621-632 ◽  
Author(s):  
Wenjin Xu ◽  
Feng Xu ◽  
Maria E. Anderson ◽  
AnnMarie E. Kotarba ◽  
Judianne Davis ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Transgenic Mice ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Β Protein

scholarly journals Synergistic effects of APOE and sex on the gut microbiome of young EFAD transgenic mice

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Juan Maldonado Weng ◽  
Ishita Parikh ◽  
Ankur Naqib ◽  
Jason York ◽  
Stefan J. Green ◽  
...  
Keyword(s):  
Machine Learning ◽  
Transgenic Mice ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
High Throughput Sequencing ◽  
Synergistic Effects ◽  
Learning Algorithms ◽  
Amyloid Β ◽  
Machine Learning Algorithms ◽  
Interactive Effects

Abstract Background Alzheimer’s disease (AD) is a fatal neurodegenerative disease. APOE4 is the greatest genetic risk factor for AD, increasing risk up to 15-fold compared to the common APOE3. Importantly, female (♀) APOE4 carriers have a greater risk for developing AD and an increased rate of cognitive decline compared to male (♂) APOE4 carriers. While recent evidence demonstrates that AD, APOE genotype, and sex affect the gut microbiome (GM), how APOE genotype and sex interact to affect the GM in AD remains unknown. Methods This study analyzes the GM of 4-month (4 M) ♂ and ♀ E3FAD and E4FAD mice, transgenic mice that overproduce amyloid-β 42 (Aβ42) and express human APOE3+/+ or APOE4+/+. Fecal microbiotas were analyzed using high-throughput sequencing of 16S ribosomal RNA gene amplicons and clustered into operational taxonomic units (OTU). Microbial diversity of the EFAD GM was compared across APOE, sex and stratified by APOE + sex, resulting in 4-cohorts (♂E3FAD, ♀E3FAD, ♂E4FAD and ♀E4FAD). Permutational multivariate analysis of variance (PERMANOVA) evaluated differences in bacterial communities between cohorts and the effects of APOE + sex. Mann-Whitney tests and machine-learning algorithms identified differentially abundant taxa associated with APOE + sex. Results Significant differences in the EFAD GM were associated with APOE genotype and sex. Stratification by APOE + sex revealed that APOE-associated differences were exhibited in ♂EFAD and ♀EFAD mice, and sex-associated differences were exhibited in E3FAD and E4FAD mice. Specifically, the relative abundance of bacteria from the genera Prevotella and Ruminococcus was significantly higher in ♀E4FAD compared to ♀E3FAD, while the relative abundance of Sutterella was significantly higher in ♂E4FAD compared to ♂E3FAD. Based on 29 OTUs identified by the machine-learning algorithms, heatmap analysis revealed significant clustering of ♀E4FAD separate from other cohorts. Conclusions The results demonstrate that the 4 M EFAD GM is modulated by APOE + sex. Importantly, the effect of APOE4 on the EFAD GM is modulated by sex, a pattern similar to the greater AD pathology associated with ♀E4FAD. While this study demonstrates the importance of interactive effects of APOE + sex on the GM in young AD transgenic mice, changes associated with the development of pathology remain to be defined.

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