Evidence map›Paper›PMID 41877131›Full record

ArticleMolecular neurodegeneration2026

Molecular characterization of humanized APOE mouse models reveals source and genotype dependent differences.

Na Wang, Gefei Yu, Zhen Wang, Alla Alnobani, Suren Jeevaratnam, Xue Zhang, Meghan McReynolds, Yuzhou Chang, Fangfang Qi, William Tauer and 14 more

Abstract read
In one paragraph

Article in Molecular neurodegeneration, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Na Wang *Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Gefei Yu *Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Zhen WangDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Alla AlnobaniDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Suren JeevaratnamDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Xue ZhangDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Meghan McReynoldsDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Yuzhou ChangDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Fangfang QiDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
William TauerDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Cassandra RosenbergDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Melissa WrenDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Tadafumi C IkezuDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Yuka A MartensDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Minghui WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Bin ZhangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Gregory W CarterThe Jackson Laboratory, Bar Harbor, ME, USA.
Michael SasnerThe Jackson Laboratory, Bar Harbor, ME, USA.
David M HoltzmanDepartment of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
Junmin PengDepartments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Long-Jun WuDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Takahisa KanekiyoDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA. kanekiyo.takahisa@mayo.edu.
Chia-Chen LiuDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA. jenfttt13@gmail.com.
Guojun BuDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA. gbu@ust.hk.

Funding

The IU/JAX Alzheimer's Disease Precision Models Center: Rat F344U54AG054345 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI Gareth R Howell · 2016 to 2026
$95.6M
Project 4 (Genetic modifiers for APOE-associated Alzheimer's disease pathogenesis)U19AG069701 · NIA · MAYO CLINIC JACKSONVILLE · PI ALISON M GOATE · 2021 to 2026
$42.0M
NIH/NIA 1RF1AG055104NIH/NIA U19AG069701NIH/NIA U54AG054345
6 · The paper itself

Abstract

backgroundHumanized APOE targeted-replacement (TR) mice are essential tools for studying apoE isoform effects in Alzheimer’s disease (AD) and other apoE-related disorders. Despite their widespread use, existing APOE mouse models, generated with different gene targeting strategies, have not been directly compared in terms of apoE isoform expression, lipid profiles, and transcriptomic signatures. Such differences could impact how we interpret APOE genotype-related outcomes, as well as related underlying molecular mechanisms.

methodsWe conducted a comprehensive molecular comparison of humanized APOE mouse models from three sources: Taconic Biosciences (TAC), the Cure Alzheimer’s Fund (CAF), and The Jackson Laboratory (JAX). We assessed apoE protein and transcript levels, peripheral plasma lipid composition, and bulk brain transcriptomics. ApoE isoform levels were evaluated by biochemical and proteomic measurements. Peripheral lipids, including low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol, and triglycerides, were also measured. We employed complementary bioinformatics analyses to evaluate brain transcriptomes and identify differentially expressed genes (DEGs) and networks based on source, APOE genotype, and sex.

resultsWe found that apoE isoforms exhibited differential levels among the three sources in the brain, liver, and plasma. Peripheral lipoproteins and lipids, including LDL, HDL, cholesterol, and triglycerides, also showed distinct concentrations in each source and genotype. Importantly, we identified distinct brain transcriptional signatures among these mouse models, which were influenced by source, APOE genotype, and sex. Finally, our analysis revealed specific differentially expressed genes and pathways impacted by source, genotype, and sex.

conclusionsOur findings highlight APOE genotype- and source-dependent variations in apoE isoform levels, lipid profiles, and molecular pathways. This study underscores the importance of consistency and caution in choosing and utilizing humanized APOE mouse models, offering molecular insights into key apoE-related outcomes.

Indexed as

Alzheimer DiseaseApolipoproteins EBrainAnimalsDisease Models, AnimalFemaleGenotypeHumansLipidsMaleMiceMice, TransgenicTranscriptomeApolipoproteins ELipidsAlzheimer’s diseaseAPOELipidsMass spectrometryMouse modelProteomicsTranscriptomics

Identifiers

PMID41877131
PMCPMC13185305

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

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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 Socratic graph.