ArticlePloS one2013
Modeling Alzheimer's disease in mouse without mutant protein overexpression: cooperative and independent effects of Aβ and tau.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Pooled it
- The 3xTg-AD Mouse Model: A Comprehensive Tool for Understanding Alzheimer's Disease.Cellular and molecular neurobiology · 2026Review
- The pathogenic APP N-terminal Val225Ala mutation alters tau protein liquid-liquid phase separation and exacerbates synaptic damage.Molecular psychiatry · 2025Article
- Inhibition of soluble epoxide hydrolase confers neuroprotection and restores microglial homeostasis in a tauopathy mouse model.Molecular neurodegeneration · 2025Article
- Whole genome-wide sequence analysis of long-lived families (Long-Life Family Study) identifies MTUS2 gene associated with late-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Discrepancy of synaptic and microtubular protein phosphorylation in the hippocampus of APP/PS1 and MAPT×P301S transgenic mice at the early stage of Alzheimer's disease.Metabolic brain disease · 2023Article
- Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) R47H Variant Causes Distinct Age- and Sex-Dependent Musculoskeletal Alterations in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Soluble brain homogenates from diverse human and mouse sources preferentially seed diffuse Aβ plaque pathology when injected into newborn mouse hosts.Free neuropathology · 2022Article
- Animal Models of Psychosis in Alzheimer Disease.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2020Review
- Article
- Importance of tau in cognitive decline as revealed by developmental exposure to lead.Toxicology letters · 2018Article
- The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade.Journal of Alzheimer's disease : JAD · 2018Review
- Article
- Practical considerations for choosing a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2017Review
- Humanized Tau Mice with Regionalized Amyloid Exhibit Behavioral Deficits but No Pathological Interaction.PloS one · 2016Article
- Folic acid inhibits tau phosphorylation through regulation of PP2A methylation in SH-SY5Y cells.The journal of nutrition, health & aging · 2015Article
- Amyloid and tau pathology of familial Alzheimer's disease APP/PS1 mouse model in a senescence phenotype background (SAMP8).Age (Dordrecht, Netherlands) · 2015Article
- Vascular and parenchymal amyloid pathology in an Alzheimer disease knock-in mouse model: interplay with cerebral blood flow.Molecular neurodegeneration · 2014Article
- Genetic suppression of transgenic APP rescues Hypersynchronous network activity in a mouse model of Alzeimer's disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Cu, Fe, and Zn isotope ratios in murine Alzheimer's disease models suggest specific signatures of amyloidogenesis and tauopathy.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAlzheimer's disease (AD), the most common cause of dementia in the elderly, has two pathological hallmarks: Aβ plaques and aggregation of hyperphosphorylated tau (p-tau). Aβ is a cleavage product of Amyloid Precursor Protein (APP). Presenilin 1 (PS1) and presenilin 2 (PS2) are the catalytic subunit of γ-secretase, which cleaves APP and mediates Aβ production. Genetic mutations in APP, PSEN1 or PSEN2 can lead to early onset of familial AD (FAD). Although mutations in the tau encoding gene MAPT leads to a subtype of frontotemporal dementia and these mutations have been used to model AD tauopathy, no MAPT mutations have been found to be associated with AD.
resultsTo model AD pathophysiology in mice without the gross overexpression of mutant transgenes, we created a humanized AD mouse model by crossing the APP and PSEN1 FAD knock-in mice with the htau mice which express wildtype human MAPT genomic DNA on mouse MAPT null background (APP/PS1/htau). The APP/PS1/htau mice displayed mild, age-dependent, Aβ plaques and tau hyperphosphorylation, thus successfully recapitulating the late-onset AD pathological hallmarks. Selected biochemical analyses, including p-tau western blot, γ-secretase activity assay, and Aβ ELISA, were performed to study the interaction between Aβ and p-tau. Subsequent behavioral studies revealed that the APP/PS1/htau mice showed reduced mobility in old ages and exaggerated fear response. Genetic analysis suggested that the fear phenotype is due to a synergic interaction between Aβ and p-tau, and it can be completely abolished by tau deletion.
conclusionThe APP/PS1/htau model represents a valuable and disease-relevant late-onset pre-clinical AD animal model because it incorporates human AD genetics without mutant protein overexpression. Analysis of the mice revealed both cooperative and independent effects of Aβ and p-tau.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.