ArticleMolecular neurodegeneration2022
Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia.
Article in Molecular neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Association between FDG- and TSPO-PET signals across human and animal studies investigating neurodegenerative conditions: a systematic review.Molecular psychiatry · 2026Pooled it
- Increased Amyloidogenic Neuronal Injury in HIV-1-infected APP-KI Alzheimer's disease mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Article
- The default mode network exhibits circuit-specific selective vulnerability despite widespread amyloid burden in an animal model of Alzheimer's disease.Nature communications · 2026Article
- Failed resolution of inflammation in intracerebral haemorrhage.Nature reviews. Neurology · 2026Review
- Assessment of early-phase [Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Article
- Prion-like transmission and propagation of human β-amyloid to the bank vole rodent model.Acta neuropathologica · 2026Article
- Impaired spatial coding and neuronal hyperactivity in the medial entorhinal cortex of aged APP knock-in mice.Cell reports · 2026Article
- Molecular mechanisms underlying amyloid lowering by aducanumab: differential and comparative effects of sex and IgG reveal the post-treatment disease brain.bioRxiv : the preprint server for biology · 2026Article
- Lipid Metabolism Reprogramming in the Aging Brain: Glial-Mediated Pathogenic Mechanisms and Translational Strategies in Neurodegeneration.International journal of molecular sciences · 2026Review
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- Article
- WSB.APP/PS1 mice develop age-dependent cerebral amyloid angiopathy, cerebrovascular dysfunction, and white matter deficits.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Kinsenoside Targets IDH1 to Restore Microglial Immune-Metabolic Homeostasis for Alzheimer's Disease Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Systems genetic dissection of brain gene expression reveals excitotoxic mechanisms of Alzheimer's disease.Molecular psychiatry · 2026Article
- Optimization and Characterization of SHIP1 Ligands for Cellular Target Engagement and Activity in Alzheimer's Disease Models.Journal of medicinal chemistry · 2026Article
- Therapeutic targeting of fibrin-microglia interactions ameliorates Alzheimer's disease-related hyperexcitability and brain network dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Glial cytokine modulation improves sleep and circadian disruption in female SAA knock-in mice of Alzheimer's-related pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Molecular signatures of resilience to Alzheimer's disease in neocortical layer 4 neurons.Nature communications · 2026Article
- TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism.Nature communications · 2026Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
48 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundGenetic mutations underlying familial Alzheimer's disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding of the immune response in the brain.
methodsWe engineered a novel App knock-in mouse model (App
resultsLeveraging multi-omics approaches, we discovered profound alteration of diverse lipids and metabolites as well as an exacerbated disease-associated transcriptomic response in microglia with high intracellular Aβ content. The App DISCUSSION: Our findings demonstrate that fibrillar Aβ in microglia is associated with lipid dyshomeostasis consistent with lysosomal dysfunction and foam cell phenotypes as well as profound immuno-metabolic perturbations, opening new avenues to further investigate metabolic pathways at play in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this novel and open-access mouse model should serve as a resource for the scientific community to investigate disease-relevant biology.
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Registered trials
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.