Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mouse Models of Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and personality changes, eventually leading to dementia. The pathological hallmarks of AD are senile plaques and neurofibrillary tangles, which comprise abnormally aggregated β-amyloid peptide (Aβ) and hyperphosphorylated tau protein. To develop preventive, diagnostic, and therapeutic strategies for AD, it is essential to establish animal models that recapitulate the pathophysiological process of AD. In this review, we will summarize the advantages and limitations of various mouse models of AD, including transgenic, knock-in, and injection models based on Aβ and tau. We will also discuss other mouse models based on neuroinflammation because recent genetic studies have suggested that microglia are crucial in the pathogenesis of AD. Although each mouse model has its advantages and disadvantages, further research on AD pathobiology will lead to the establishment of more accurate mouse models, and accelerate the development of innovative therapeutics.

SUBMITTER: Yokoyama M

PROVIDER: S-EPMC9254908 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Mouse Models of Alzheimer's Disease.

Yokoyama Miyabishara M Kobayashi Honoka H Tatsumi Lisa L Tomita Taisuke T

Frontiers in molecular neuroscience 20220621

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and personality changes, eventually leading to dementia. The pathological hallmarks of AD are senile plaques and neurofibrillary tangles, which comprise abnormally aggregated β-amyloid peptide (Aβ) and hyperphosphorylated tau protein. To develop preventive, diagnostic, and therapeutic strategies for AD, it is essential to establish animal models that recapitulate the pathophysiological process of AD. In this re ...[more]

PMID: 35799899

Similar Datasets

Proteomics of Alzheimer's Disease mouse models

Project description:Alzheimer’s disease (AD) is a neurodegenerative disease displaying plaques formed by the neurotoxic amyloid β-peptide (Aβ) and intracellular neurofibrillary tangles consisting of protein tau. However, how these pathologies relates to the massive neuronal death that occurs in AD brains remain elusive. To identify proteins, the levels of which are affected by increased Aβ levels, we performed a proteomic analysis of the AD mouse model APPsw and compared it to that of APPsw mice lacking the major Aβ degrading enzyme neprilysin. This was achieved by establishing an LC-MS/MS method to analyze brain homogenate, using an 18O-labeled internal standard to accurately quantify the protein levels. By this approach we identified approximately 600 proteins and could quantify the levels of 300 of these. Interestingly, several proteins, including some not previously reported to be associated with AD, were identified. The relevance of these proteins for AD warrants further research.

2015-07-29 | PXD000968 | Pride

Neuroinflammation in mouse models of Alzheimer's disease.

Project description:Alzheimer's disease (AD) is the most common type of neurocognitive disorder. Although both amyloid ? peptide deposition and neurofibrillary tangle formation in the AD brain have been established as pathological hallmarks of the disease, many other factors contribute in a complex manner to the pathogenesis of AD before clinical symptoms of the disease become apparent. Longitudinal pathophysiological processes cause patients' brains to exist in a state of chronic neuroinflammation, with glial cells acting as key regulators of the neuroinflammatory state. However, the detailed molecular and cellular mechanisms of glial function underlying AD pathogenesis remain elusive. Furthermore, recent studies have shown that peripheral inflammatory conditions affect glial cells in the brain through a process of neuroimmune communication. Such disease complexities make it difficult for the pathogenesis of AD to be understood, and impede the development of effective therapeutic strategies to combat the disease. Relevant AD animal models are thus likely to serve as a key resource to overcome many of these issues. Furthermore, as the pathogenesis of AD might be linked to conditions both within the brain as well as peripherally, it might become necessary for AD to be studied as a whole-body disorder. The present review aimed to summarize insights regarding current AD research, and share perspectives for understanding glial function in the context of the pathogenesis of AD.

| S-EPMC6282739 | biostudies-other

Can mouse models mimic sporadic Alzheimer's disease?

Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia worldwide. As age is the main risk factor, > 97% of all AD cases are of sporadic origin, potentiated by various risk factors associated with life style and starting at an age > 60 years. Only < 3% of AD cases are of genetic origin caused by mutations in the amyloid precursor protein or Presenilins 1 or 2, and symptoms already start at an age < 30 years. In order to study progression of AD, as well as therapeutic strategies, mouse models are state-of-the-art. So far many transgenic mouse models have been developed and used, with mutations in the APP or presenilin or combinations (3×Tg, 5×Tg). However, such transgenic mouse models more likely mimic the genetic form of AD and no information can be given how sporadic forms develop. Several risk genes, such as Apolipoprotein E4 and TREM-2 enhance the risk of sporadic AD, but also many risk factors associated with life style (e.g., diabetes, hypercholesterolemia, stress) may play a role. In this review we discuss the current situation regarding AD mouse models, and the problems to develop a sporadic mouse model of AD.

| S-EPMC6921354 | biostudies-literature

Updates on mouse models of Alzheimer's disease.

Project description:Alzheimer's disease (AD) is the most common neurodegenerative disease in the United States (US). Animal models, specifically mouse models have been developed to better elucidate disease mechanisms and test therapeutic strategies for AD. A large portion of effort in the field was focused on developing transgenic (Tg) mouse models through over-expression of genetic mutations associated with familial AD (FAD) patients. Newer generations of mouse models through knock-in (KI)/knock-out (KO) or CRISPR gene editing technologies, have been developed for both familial and sporadic AD risk genes with the hope to more accurately model proteinopathies without over-expression of human AD genes in mouse brains. In this review, we summarized the phenotypes of a few commonly used as well as newly developed mouse models in translational research laboratories including the presence or absence of key pathological features of AD such as amyloid and tau pathology, synaptic and neuronal degeneration as well as cognitive and behavior deficits. In addition, advantages and limitations of these AD mouse models have been elaborated along with discussions of any sex-specific features. More importantly, the omics data from available AD mouse models have been analyzed to categorize molecular signatures of each model reminiscent of human AD brain changes, with the hope to guide future selection of most suitable models for specific research questions to be addressed in the AD field.

| S-EPMC10926682 | biostudies-literature

Proteomics of Alzheimer's Disease mouse models - control dataset

Project description:Alzheimer’s disease (AD) is a neurodegenerative disease displaying plaques formed by the neurotoxic amyloid β-peptide (Aβ), and intracellular neurofibrillary tangles consisting of protein tau. However, how these pathologies relates to the massive neuronal death that occurs in AD brains remain elusive. Neprilysin is the major A degrading enzyme and a lack thereof increases A levels in the brain twofold. To identify altered protein expression levels induced by increased Aβ levels, we performed a proteomic analysis of the brain of the AD mouse model APPsw and compared it to that of APPsw mice lacking neprilysin. To this end we established an LC-MS/MS method to analyze brain homogenate, using an 18O-labeled internal standard to accurately quantify the protein levels. To distinguish between alterations in protein levels directly caused by increased A levels and those induced by neprilysin deficiency independently of A, the brain proteome of neprilysin deficient APPsw mice was compared to that of neprilysin deficient mice. By this approach we identified approximately 600 proteins and could quantify the levels of 300 of these. Pathway analysis showed that many of the proteins with altered expression were involved in neurological disorders, and that tau, presenilin and APP were key regulators in the identified networks. The data have been deposited to the ProteomeXchange Consortium with identifier PXD000968. Interestingly, the levels of several proteins, including some not previously reported to be associated with AD, were associated with increased A levels.

2015-07-29 | PXD001786 | Pride

Transgenic Mouse Models of Alzheimer's Disease: An Integrative Analysis.

Project description:Alzheimer's disease (AD) constitutes the most prominent form of dementia among elderly individuals worldwide. Disease modeling using murine transgenic mice was first initiated thanks to the discovery of heritable mutations in amyloid precursor protein (APP) and presenilins (PS) genes. However, due to the repeated failure of translational applications from animal models to human patients, along with the recent advances in genetic susceptibility and our current understanding on disease biology, these models have evolved over time in an attempt to better reproduce the complexity of this devastating disease and improve their applicability. In this review, we provide a comprehensive overview about the major pathological elements of human AD (plaques, tauopathy, synaptic damage, neuronal death, neuroinflammation and glial dysfunction), discussing the knowledge that available mouse models have provided about the mechanisms underlying human disease. Moreover, we highlight the pros and cons of current models, and the revolution offered by the concomitant use of transgenic mice and omics technologies that may lead to a more rapid improvement of the present modeling battery.

| S-EPMC9142061 | biostudies-literature

Brain cellular senescence in mouse models of Alzheimer's disease.

Project description:The accumulation of senescent cells contributes to aging pathologies, including neurodegenerative diseases, and its selective removal improves physiological and cognitive function in wild-type mice as well as in Alzheimer's disease (AD) models. AD models recapitulate some, but not all components of disease and do so at different rates. Whether brain cellular senescence is recapitulated in some or all AD models and whether the emergence of cellular senescence in AD mouse models occurs before or after the expected onset of AD-like cognitive deficits in these models are not yet known. The goal of this study was to identify mouse models of AD and AD-related dementias that develop measurable markers of cellular senescence in brain and thus may be useful to study the role of cellular senescence in these conditions. We measured the levels of cellular senescence markers in the brains of P301S(PS19), P301L, hTau, and 3xTg-AD mice that model amyloidopathy and/or tauopathy in AD and related dementias and in wild-type, age-matched control mice for each strain. Expression of cellular senescence markers in brains of transgenic P301L and 3xTg-AD mice was largely indistinguishable from that in WT control age-matched mice. In contrast, markers of cellular senescence were differentially increased in brains of transgenic hTau and P301S(PS19) mice as compared to WT control mice before the onset of AD-like cognitive deficits. Taken together, our data suggest that P301S(PS19) and hTau mice may be useful models for the study of brain cellular senescence in tauopathies including, but not limited to, AD.

| S-EPMC9135905 | biostudies-literature

Liver Bile Acid Changes in Mouse Models of Alzheimer's Disease.

Project description:Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. It is hypothesized to develop due to the dysfunction of two major proteins, amyloid-β (Aβ) and microtubule-associated protein, tau. Evidence supports the involvement of cholesterol changes in both the generation and deposition of Aβ. This study was performed to better understand the role of liver cholesterol and bile acid metabolism in the pathophysiology of AD. We used male and female wild-type control (C57BL/6J) mice to compare to two well-characterized amyloidosis models of AD, APP/PS1, and AppNL-G-F. Both conjugated and unconjugated primary and secondary bile acids were quantified using UPLC-MS/MS from livers of control and AD mice. We also measured cholesterol and its metabolites and identified changes in levels of proteins associated with bile acid synthesis and signaling. We observed sex differences in liver cholesterol levels accompanied by differences in levels of synthesis intermediates and conjugated and unconjugated liver primary bile acids in both APP/PS1 and AppNL-G-F mice when compared to controls. Our data revealed fundamental deficiencies in cholesterol metabolism and bile acid synthesis in the livers of two different AD mouse lines. These findings strengthen the involvement of liver metabolism in the pathophysiology of AD.

| S-EPMC8303891 | biostudies-literature

Adaptable toolbox to characterize Alzheimer's disease pathology in mouse models.

Project description:Here, we describe a highly adaptable toolbox for characterizing and analyzing molecular and histopathological changes in Alzheimer's disease (AD) mouse models. We detail optimized and streamlined approaches from sample preparation to image analysis to facilitate reproducible analyses. We also describe the extraction and measurement of the soluble Aβ level by sandwich ELISA in the cortex and hippocampus of AD mouse models before and after plaque deposition. Finally, we outline the steps for image quantification and analysis using Imaris and ImageJ. For complete details on the use and execution of this protocol, please refer to Huang et al. (2021).1.

| S-EPMC9722779 | biostudies-literature