P.1.01 Modification of histone H3 and H4 in the brain of Tg2576 transgenic mice – implications for Alzheimer's disease

2007 ◽  
Vol 17 ◽  
pp. S2-S3
Author(s):  
C. Unger ◽  
C.M. Hernandez ◽  
A. Nordberg ◽  
J.D. Sweatt
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Histone H3 ◽  
The Brain

scholarly journals Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Xin-Yi Lu ◽  
Shun Huang ◽  
Qu-Bo Chen ◽  
Dapeng Zhang ◽  
Wanyan Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Mrna Expression ◽  
Insulin Degrading Enzyme ◽  
Antidiabetic Drug ◽  
Degrading Enzyme ◽  
Expression Levels ◽  
The Brain ◽  
Mrna Expression Levels

Alzheimer’s disease (AD) is the most common neurodegenerative disease. The accumulation of amyloid beta (Aβ) is the main pathology of AD. Metformin, a well-known antidiabetic drug, has been reported to have AD-protective effect. However, the mechanism is still unclear. In this study, we tried to figure out whether metformin could activate insulin-degrading enzyme (IDE) to ameliorate Aβ-induced pathology. Morris water maze and Y-maze results indicated that metformin could improve the learning and memory ability in APPswe/PS1dE9 (APP/PS1) transgenic mice. 18F-FDG PET-CT result showed that metformin could ameliorate the neural dysfunction in APP/PS1 transgenic mice. PCR analysis showed that metformin could effectively improve the mRNA expression level of nerve and synapse-related genes (Syp, Ngf, and Bdnf) in the brain. Metformin decreased oxidative stress (malondialdehyde and superoxide dismutase) and neuroinflammation (IL-1β and IL-6) in APP/PS1 mice. In addition, metformin obviously reduced the Aβ level in the brain of APP/PS1 mice. Metformin did not affect the enzyme activities and mRNA expression levels of Aβ-related secretases (ADAM10, BACE1, and PS1). Meanwhile, metformin also did not affect the mRNA expression levels of Aβ-related transporters (LRP1 and RAGE). Metformin increased the protein levels of p-AMPK and IDE in the brain of APP/PS1 mice, which might be the key mechanism of metformin on AD. In conclusion, the well-known antidiabetic drug, metformin, could be a promising drug for AD treatment.

P3-149: Protein expression in the brain of transgenic mice models of Alzheimer's disease

2011 ◽  
Vol 7 ◽  
pp. S564-S564
Author(s):  
Manuela Fritsch ◽  
Daniela Volke ◽  
Ralf Hoffmann ◽  
David Singer
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Protein Expression ◽  
The Brain

scholarly journals Quinacrine directly dissociates amyloid plaques in the brain of 5XFAD transgenic mouse model of Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sohui Park ◽  
Hye Yun Kim ◽  
Hyun-A Oh ◽  
Jisu Shin ◽  
In Wook Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Weight ◽  
Transgenic Mice ◽  
Cortical Neurons ◽  
Amyloid Β ◽  
Synaptic Function ◽  
Western Blots ◽  
Aβ Fibrils ◽  
The Brain

AbstractAlzheimer’s disease (AD) is the most common type of dementia characterized by the abnormal accumulation of amyloid-β (Aβ) in the brain. Aβ misfolding is associated with neuroinflammation and synaptic dysfunction, leading to learning and memory deficits. Therefore, Aβ production and aggregation have been one of the most popular drug targets for AD. Failures of drug candidates regulating the aforementioned Aβ cascade stimulated development of immunotherapy agents for clearance of accumulated Aβ in the brain. Here, we report that quinacrine, a blood–brain barrier penetrating antimalarial chemical drug, dissociates Aβ plaques in the brain of AD transgenic mice. When co-incubated with pre-formed Aβ fibrils, quinacrine decreased thioflavin T-positive β-sheets in vitro, on top of its inhibitory function on the fibril formation. We confirmed that quinacrine induced dissociation of high-molecular-weight Aβ aggregates into low-molecular-weight species by dot blots in association with size cut-off filtrations. Quinacrine was then administered to adult 5XFAD transgenic mice via weekly intravenous injections for 6 weeks, and we found a significant reduction of Aβ plaques and astrocytosis in their cortex and hippocampus. In western blots of quinacrine-administered mouse brains, amelioration of AD-related biomarkers, glial fibrillary acidic protein, postsynaptic protein 95, phosphorylated cAMP response element-binding protein, phosphorylated c-Jun N-terminal kinase were observed. Lastly, quinacrine-stimulated dissociation of misfolded aggregates induced recovery of synaptic function associated with Aβ in excitatory post-synaptic current recordings of primary rat cortical neurons treated with Aβ aggregates and quinacrine. Collectively, quinacrine can directly dissociate Aβ fibrils and alleviate decreased synaptic functions.

scholarly journals Region-specific metabolic alterations in the brain of the APP/PS1 transgenic mice of Alzheimer's disease

2014 ◽  
Vol 1842 (12) ◽  
pp. 2395-2402 ◽  
Author(s):  
Raúl González-Domínguez ◽  
Tamara García-Barrera ◽  
Javier Vitorica ◽  
José Luis Gómez-Ariza
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Metabolic Alterations ◽  
The Brain

scholarly journals Pinpointing Brain TREM2 Levels in Two Mouse Models of Alzheimer’s Disease

2021 ◽  
Author(s):  
Silvio R. Meier ◽  
Dag Sehlin ◽  
Greta Hultqvist ◽  
Stina Syvänen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Mouse Models ◽  
Microglial Activation ◽  
Bispecific Antibody ◽  
Ex Vivo ◽  
Transgenic Animals ◽  
The Brain

Abstract Purpose The triggering receptor expressed on myeloid cells 2 (TREM2) is expressed by brain microglia. Microglial activation, as observed in Alzheimer’s disease (AD) as well as in transgenic mice expressing human amyloid-beta, appears to increase soluble TREM2 (sTREM2) levels in CSF and brain. In this study, we used two different transgenic mouse models of AD pathology and investigated the potential of TREM2 to serve as an in vivo biomarker for microglial activation in AD. Procedures We designed and generated a bispecific antibody based on the TREM2-specific monoclonal antibody mAb1729, fused to a single-chain variable fragment of the transferrin receptor binding antibody 8D3. The 8D3-moiety enabled transcytosis of the whole bispecific antibody across the blood-brain barrier. The bispecific antibody was radiolabeled with I-125 (ex vivo) or I-124 (PET) and administered to transgenic AD and wild-type (WT) control mice. Radioligand retention in the brain of transgenic animals was compared to WT mice by isolation of brain tissue at 24 h or 72 h, or with in vivo PET at 24 h, 48 h, and 72 h. Intrabrain distribution of radiolabeled mAb1729-scFv8D3CL was further studied by autoradiography, while ELISA was used to determine TREM2 brain concentrations. Results Transgenic animals displayed higher total exposure, calculated as the AUC based on SUV determined at 24h, 48h, and 72h post injection, of PET radioligand [124I]mAb1729-scFv8D3CL than WT mice. However, differences were not evident in single time point PET images or SUVs. Ex vivo autoradiography confirmed higher radioligand concentrations in cortex and thalamus in transgenic mice compared to WT, and TREM2 levels in brain homogenates were considerably higher in transgenic mice compared to WT. Conclusion Antibody-based radioligands, engineered to enter the brain, may serve as PET radioligands to follow changes of TREM2 in vivo, but antibody formats with faster systemic clearance to increase the specific signal in relation to that from blood in combination with antibodies showing higher affinity for TREM2 must be developed to further progress this technique for in vivo use.

scholarly journals Fiber Tracts Anomalies in APPxPS1 Transgenic Mice Modeling Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
H. Chen ◽  
S. Epelbaum ◽  
B. Delatour
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Clinical Symptoms ◽  
Anterior Commissure ◽  
Fiber Tract ◽  
Fiber Tracts ◽  
Age Related ◽  
The Impact ◽  
The Brain

Amyloid beta (A) peptides are known to accumulate in the brain of patients with Alzheimer's disease (AD). However, the link between brain amyloidosis and clinical symptoms has not been elucidated and could be mediated by secondary neuropathological alterations such as fiber tracts anomalies. In the present study, we have investigated the impact of A overproduction in APPxPS1 transgenic mice on the integrity of forebrain axonal bundles (corpus callosum and anterior commissure). We found evidence of fiber tract volume reductions in APPxPS1 mice that were associated with an accelerated age-related loss of axonal neurofilaments and a myelin breakdown. The severity of these defects was neither correlated with the density of amyloid plaques nor associated with cell neurodegeneration. Our data suggest that commissural fiber tract alterations are present in A-overproducing transgenic mice and that intracellular A accumulation preceding extracellular deposits may act as a trigger of such morphological anomalies.

scholarly journals Immunocytochemical Characterization of Alzheimer’s Disease Hallmarks in APP/PS1 Transgenic Mice Treated with a New Anti-Amyloid-β Vaccine

2014 ◽  
Vol 2 ◽  
Author(s):  
Ivan Carrera ◽  
Ignacio Etcheverria ◽  
Yi Li ◽  
Lucia Fernandez-Novoa ◽  
Valter Lombardi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Inflammatory Responses ◽  
Passive Immunization ◽  
New Approach ◽  
Double Transgenic Mouse ◽  
Sphingosine 1 Phosphate ◽  
The Brain

Introduction: APP/PS1 double-transgenic mouse models of Alzheimer’s disease (AD), which overexpress mutated forms of the gene for the human amyloid precursor protein (APP) and presenilin 1 (PS1), have provided robust neuropathological hallmarks of an AD-like pattern at early ages. This study aimed to characterize immunocytochemical patterns of the AD mouse brain, which is treated with the EB101 vaccine, as a model for human AD.Material and methods: In this novel vaccine, a new approach has been taken to circumvent past failures with Aβ vaccines by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol).Results: Our findings showed that the administration of amyloid-β1−42 (Aβ) and sphingosine-1-phosphate emulsified in liposome complex (EB101) to APP/PS1 mice before the onset of Aβ brain deposition (at 7 weeks of age) and/or at an older age (35 weeks of age) can be effective in both halting the progression and clearing the AD-like neuropathological hallmarks. In addition, passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus) in the brain of treated mice was notably reduced.Conclusion: These results provide strong evidence that immunization with the EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice.

scholarly journals PET Imaging of Neutrophils Infiltration in Alzheimer's Disease Transgenic Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Yanyan Kong ◽  
Kawai Liu ◽  
Tao Hua ◽  
Chencheng Zhang ◽  
Bomin Sun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Pet Imaging ◽  
Rt Pcr ◽  
Neutrophil Accumulation ◽  
Triple Mutant ◽  
Western Blot Assay ◽  
The Status ◽  
The Brain

Neutrophils are important components in the innate immune system. Neutrophil hyperactivation is regarded as a characteristic of Alzheimer's disease (AD). But in vivo imaging tools observing neutrophil activity in AD dynamically is lacking. This study aimed to identify neutrophil infiltration in AD transgenic mice. We used the AD triple-mutant transgenic mouse model and identified the genotype with RT-PCR. Behavioral experiments including an open-field test, a Morris water maze, and a Y-maze test were performed to evaluate the status of this AD model. 18F-AV45, 18F-PM-PBB3, 68Ga-PEG-cFLFLFK, and 18F-DPA714 were synthesized according to previous reports. We employed microPET to detect tracer uptake in the AD model and the control mice at different stages. Western blotting was used to observe the expression of functional proteins. We proved the successful establishment of AD models by RT-PCR, behavioral tests, and 18F-AV45 and 18F-PM-PBB3 PET imaging. We found an increased neutrophil accumulation in the brains of the AD mice through 68Ga-PEG-cFLFLFK PET imaging and Western blot assay. Our studies also demonstrated an elevated level of CAP37, which is produced by neutrophils, in the AD brain, and treatment with CAP37 promoted the expression of Iba1, iNOS, and COX-2 in BV2 cultures. Furthermore, our 18F-DPA714 PET imaging studies verified the raised activation of microglia in the brain of transgenic AD mice. Collectively, our findings indicate the increased activity of neutrophils in the brain and heart of AD model mice, 68Ga-PEG-cFLFLFK PET imaging represents a sensitive method to observe the status of neutrophils in AD, and infiltrated neutrophils can induce the activation of microglia by releasing CAP37 and blocking the activity of neutrophils may be beneficial for the control of AD progression.

Longitudinal Changes in Individual BrainAGE in Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

GeroPsych ◽  
2012 ◽  
Vol 25 (4) ◽  
pp. 235-245 ◽  
Author(s):  
Katja Franke ◽  
Christian Gaser
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Aging ◽  
Brain Aging ◽  
Elderly Subjects ◽  
Additional Increase ◽  
Longitudinal Changes ◽  
Novel Method ◽  
The Brain

We recently proposed a novel method that aggregates the multidimensional aging pattern across the brain to a single value. This method proved to provide stable and reliable estimates of brain aging – even across different scanners. While investigating longitudinal changes in BrainAGE in about 400 elderly subjects, we discovered that patients with Alzheimer’s disease and subjects who had converted to AD within 3 years showed accelerated brain atrophy by +6 years at baseline. An additional increase in BrainAGE accumulated to a score of about +9 years during follow-up. Accelerated brain aging was related to prospective cognitive decline and disease severity. In conclusion, the BrainAGE framework indicates discrepancies in brain aging and could thus serve as an indicator for cognitive functioning in the future.

Sign in / Sign up

Export Citation Format

Share Document