Circadian wheel running behavior is altered in an APP/E4 mouse model of late onset Alzheimer's disease

2017 ◽  
Vol 182 ◽  
pp. 137-142 ◽  
Author(s):  
Katelyn N. Boggs ◽  
Peter A. Kakalec ◽  
Meghann L. Smith ◽  
Stefanie N. Howell ◽  
Jane M. Flinn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Wheel Running ◽  
Late Onset

scholarly journals Hallmarks of late‐onset Alzheimer’s disease in a humanized mouse model

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Kevin P. Kotredes ◽  
Christoph Preuss ◽  
Ravi S. Pandey ◽  
Paul R. Territo ◽  
Adrian L. Oblak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Late Onset ◽  
Humanized Mouse ◽  
Humanized Mouse Model

scholarly journals Amyloid precursor protein (APP) knock‐in mouse model recapitulates transciptomic signature in human late‐onset Alzheimer’s disease

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Marco Antônio De Bastiani ◽  
Eduardo R. Zimmer ◽  
Stefania Forner ◽  
Alessandra Cadete Martini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Precursor Protein ◽  
Late Onset ◽  
Precursor Protein

scholarly journals Voluntary running does not reduce neuroinflammation or improve non-cognitive behavior in the 5xFAD mouse model of Alzheimer’s disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Martina Svensson ◽  
Emelie Andersson ◽  
Oscar Manouchehrian ◽  
Yiyi Yang ◽  
Tomas Deierborg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Wheel Running ◽  
Synaptic Proteins ◽  
Voluntary Wheel Running ◽  
Voluntary Running ◽  
5Xfad Mouse ◽  
5Xfad Mice ◽  
Voluntary Wheel

AbstractPhysical exercise has been suggested to reduce the risk of developing Alzheimer’s disease (AD) as well as ameliorate the progression of the disease. However, we recently published results from two large epidemiological studies showing no such beneficial effects on the development of AD. In addition, long-term, voluntary running in the 5xFAD mouse model of AD did not affect levels of soluble amyloid beta (Aβ), synaptic proteins or cognitive function. In this follow-up study, we investigate whether running could impact other pathological aspects of the disease, such as insoluble Aβ levels, the neuroinflammatory response and non-cognitive behavioral impairments. We investigated the effects of 24 weeks of voluntary wheel running in female 5xFAD mice (n = 30) starting at 2–3 months of age, before substantial extracellular plaque formation. Running mice developed hindlimb clasping earlier (p = 0.009) compared to sedentary controls. Further, running exacerbated the exploratory behavior in Elevated plus maze (p = 0.001) and anxiety in Open field (p = 0.024) tests. Additionally, microglia, cytokines and insoluble Aβ levels were not affected. Taken together, our findings suggest that voluntary wheel running is not a beneficial intervention to halt disease progression in 5xFAD mice.

Wheel-running in a transgenic mouse model of Alzheimer's disease: Protection or symptom?

2008 ◽  
Vol 190 (1) ◽  
pp. 74-84 ◽  
Author(s):  
Helene Richter ◽  
Oliver Ambrée ◽  
Lars Lewejohann ◽  
Arne Herring ◽  
Kathy Keyvani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Wheel Running ◽  
Transgenic Mouse Model ◽  
Model Of Alzheimer’S Disease

scholarly journals Computational Interspecies Translation Between Alzheimer’s Disease Mouse Models and Human Subjects Identifies Innate Immune Complement, TYROBP, and TAM Receptor Agonist Signatures, Distinct From Influences of Aging

2021 ◽  
Vol 15 ◽  
Author(s):  
Meelim J. Lee ◽  
Chuangqi Wang ◽  
Molly J. Carroll ◽  
Douglas K. Brubaker ◽  
Bradley T. Hyman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Mouse Models ◽  
Late Onset ◽  
Innate Immune ◽  
Cytokine Signaling ◽  
Preclinical Research ◽  
Human Patient ◽  
Receptor Family

Mouse models are vital for preclinical research on Alzheimer’s disease (AD) pathobiology. Many traditional models are driven by autosomal dominant mutations identified from early onset AD genetics whereas late onset and sporadic forms of the disease are predominant among human patients. Alongside ongoing experimental efforts to improve fidelity of mouse model representation of late onset AD, a computational framework termed Translatable Components Regression (TransComp-R) offers a complementary approach to leverage human and mouse datasets concurrently to enhance translation capabilities. We employ TransComp-R to integratively analyze transcriptomic data from human postmortem and traditional amyloid mouse model hippocampi to identify pathway-level signatures present in human patient samples yet predictive of mouse model disease status. This method allows concomitant evaluation of datasets across different species beyond observational seeking of direct commonalities between the species. Additional linear modeling focuses on decoupling disease signatures from effects of aging. Our results elucidated mouse-to-human translatable signatures associated with disease: excitatory synapses, inflammatory cytokine signaling, and complement cascade- and TYROBP-based innate immune activity; these signatures all find validation in previous literature. Additionally, we identified agonists of the Tyro3 / Axl / MerTK (TAM) receptor family as significant contributors to the cross-species innate immune signature; the mechanistic roles of the TAM receptor family in AD merit further dedicated study. We have demonstrated that TransComp-R can enhance translational understanding of relationships between AD mouse model data and human data, thus aiding generation of biological hypotheses concerning AD progression and holding promise for improved preclinical evaluation of therapies.

scholarly journals β-Hydroxybutyrate inhibits inflammasome activation to attenuate Alzheimer’s disease pathology

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Daniel C. Shippy ◽  
Connor Wilhelm ◽  
Patel A. Viharkumar ◽  
Thomas J. Raife ◽  
Tyler K. Ulland
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Nlrp3 Inflammasome ◽  
Ketone Bodies ◽  
Late Onset ◽  
Inflammasome Activation ◽  
Age Related ◽  
Nlrp3 Inflammasome Activation ◽  
5Xfad Mouse

Abstract Alzheimer’s disease (AD) is a progressive, late-onset dementia with no effective treatment available. Recent studies suggest that AD pathology is driven by age-related changes in metabolism. Alterations in metabolism, such as placing patients on a ketogenic diet, can alter cognition by an unknown mechanism. One of the ketone bodies produced as a result of ketogenesis, β-hydroxybutyrate (BHB), is known to inhibit NLRP3 inflammasome activation. Therefore, we tested if BHB inhibition of the NLRP3 inflammasome reduces overall AD pathology in the 5XFAD mouse model of AD. Here, we find BHB levels are lower in red blood cells and brain parenchyma of AD patients when compared with non-AD controls. Furthermore, exogenous BHB administration reduced plaque formation, microgliosis, apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) speck formation, and caspase-1 activation in the 5XFAD mouse model of AD. Taken together, our findings demonstrate that BHB reduces AD pathology by inhibiting NLRP3 inflammasome activation. Additionally, our data suggest dietary or pharmacological approaches to increase BHB levels as promising therapeutic strategies for AD.

P4-028: CHARACTERIZING THE APOE4/TREM2*R47H MOUSE MODEL FOR LATE ONSET ALZHEIMER'S DISEASE

2006 ◽  
Vol 14 (7S_Part_27) ◽  
pp. P1444-P1444
Author(s):  
Harriet M. Williams ◽  
Adrian L. Oblak ◽  
Rita O'Rourke ◽  
Rebecca Buchanan ◽  
Kelly J. Keezer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Late Onset

scholarly journals Comprehensive Evaluation of the 5XFAD Mouse Model for Preclinical Testing Applications: A MODEL-AD Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Adrian L. Oblak ◽  
Peter B. Lin ◽  
Kevin P. Kotredes ◽  
Ravi S. Pandey ◽  
Dylan Garceau ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Mouse Model ◽  
Biochemical Characterization ◽  
Late Onset ◽  
Therapeutic Interventions ◽  
Preclinical Testing ◽  
5Xfad Mouse

The ability to investigate therapeutic interventions in animal models of neurodegenerative diseases depends on extensive characterization of the model(s) being used. There are numerous models that have been generated to study Alzheimer’s disease (AD) and the underlying pathogenesis of the disease. While transgenic models have been instrumental in understanding AD mechanisms and risk factors, they are limited in the degree of characteristics displayed in comparison with AD in humans, and the full spectrum of AD effects has yet to be recapitulated in a single mouse model. The Model Organism Development and Evaluation for Late-Onset Alzheimer’s Disease (MODEL-AD) consortium was assembled by the National Institute on Aging (NIA) to develop more robust animal models of AD with increased relevance to human disease, standardize the characterization of AD mouse models, improve preclinical testing in animals, and establish clinically relevant AD biomarkers, among other aims toward enhancing the translational value of AD models in clinical drug design and treatment development. Here we have conducted a detailed characterization of the 5XFAD mouse, including transcriptomics, electroencephalogram, in vivo imaging, biochemical characterization, and behavioral assessments. The data from this study is publicly available through the AD Knowledge Portal.

Voluntary Wheel Running Reduces Amyloid-β42 and Rescues Behavior in Aged Tg2576 Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 73 (1) ◽  
pp. 359-374 ◽  
Author(s):  
Nikita Francis ◽  
Lisa S. Robison ◽  
Dominique L. Popescu ◽  
Michalis Michaelos ◽  
Joshua Hatfield ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Wheel Running ◽  
Tg2576 Mouse ◽  
Voluntary Wheel Running ◽  
Model Of Alzheimer’S Disease ◽  
Voluntary Wheel
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