APOE4 to APOE2 allelic switching in mice improves Alzheimer's disease-related metabolic signatures, neuropathology and cognition.

doi:10.1038/s41593-025-02094-y

Loading publication...

Noodle always counts identifier-free feature events for service operation. With your permission, Google Analytics can also estimate audience and engagement. Search text, publication identifiers, cookies, IP addresses and browser fingerprints are never included in Noodle's first-party event counters.

Privacy details

Community

Back to search

Article

APOE4 to APOE2 allelic switching in mice improves Alzheimer's disease-related metabolic signatures, neuropathology and cognition.

Nature neuroscience - 1 Dec 2025

Golden Lesley R, Siano Dahlia S, Stephens Isaiah O, MacLean Steven M, Saito Kai, Nolt Georgia L, Funnell Jessica L, Pallerla Akhil V, Lee Sangderk, Smith Cathryn, Chen Jing, Zhu Haining, Voy Clairity, Whitus Callie M, Hernandez Gabriela, Farmer Brandon C, Pandya Kumar, Cowley Dale O, Macauley Shannon L, Gordon Scott M, Morganti Josh M, Johnson Lance A

Abstract excerpt

Compared to individuals carrying two copies of the ε4 allele of apolipoprotein E (APOE), ε2 homozygotes have an approximate 99% reduction in late-onset Alzheimer's disease (AD) risk. Here we develop a knock-in model that allows for an inducible 'switch' between risk and protective alleles (APOE4s2). Gene expression and proteomic analyses confirm that APOE4s2 mice synthesize E4 at baseline and E2 after tamoxifen...

Read the complete abstract on PubMed

Topics

Share this publication in a Topic to start or enrich a Post.

Share to Alzheimer Disease

Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Share to Apolipoprotein E2

Share to Apolipoprotein E4

Share to Astrocytes

Share to Cognition

Share to Gene Knock-In Techniques

Share to Mice, Transgenic

Share to Transcriptome

Source

Open in PubMed Open full text

Identifiers

PMID: 41219507
DOI: 10.1038/s41593-025-02094-y
PMCID: PMC12672373

Genes

APOE

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 8 Sept 2026.

Related research

Semantic proximity does not establish scientific evidence.

Research trail→

Click a neighbor to travelStep 1 · 12 closest

APOE4 to APOE2 allelic switching in mice improves Alzheimer's disease-related metabolic signatures, neuropathology and cognition.PMID 41219507Read ↗

APOE4 drives transcriptional heterogeneity and maladaptive immunometabolic responses of astrocytesSemantic proximity Read ↗

APOE4 Lowers Energy Expenditure and Impairs Glucose Oxidation by Increasing Flux through Aerobic GlycolysisSemantic proximity Read ↗

APOE2, E3 and E4 differentially modulate cellular homeostasis, cholesterol metabolism and inflammatory response in isogenic iPSC-derived astrocytesSemantic proximity Read ↗

APOE2, E3, and E4 differentially modulate cellular homeostasis, cholesterol metabolism, and inflammatory response in isogenic iPSC-derived astrocytes.Semantic proximity Read ↗

AAV-based temporal APOE4-to-APOE2 replacement reveals rebound adaptation and RAB24-mediated Aβ and cholesterol dysregulationSemantic proximity Read ↗

APOE4 drives widespread changes to the hepatic proteome and alters metabolic functionSemantic proximity Read ↗

Proteomic and metabolic profiling reveals APOE4 -dependent shifts in whole brain, neuronal, and astrocytic mitochondrial function and glycolysisSemantic proximity Read ↗

Recombinant sialylated ApoE2 suppresses ApoE4 and sex-specifically strengthens brain metabolism and cognition in ApoE4 miceSemantic proximity Read ↗

Differential Regulation of APOE4-Mediated Astrocytic Lipid Metabolism by BMP Signaling Exacerbates Alzheimer’s Disease Pathologies in NeuronsSemantic proximity Read ↗

Cholesterol and matrisome pathways dysregulated in human APOE ε4 gliaSemantic proximity Read ↗

Opposing effects of viral mediated brain expression of apolipoprotein E2 (apoE2) and apoE4 on apoE lipidation and Aβ metabolism in apoE4-targeted replacement miceSemantic proximity Read ↗

ApoE4-Induced Cholesterol Dysregulation and Its Brain Cell Type-Specific Implications in the Pathogenesis of Alzheimer's Disease.Semantic proximity Read ↗

⌁Select a neighboring publication to make it the new centre.