Evidence map›Paper›PMID 40011916›Full record

ArticleCell communication and signaling : CCS2025

ApoE2 affects insulin signaling in the hippocampus and spatial cognition of aged mice in a sex-dependent manner.

Yu Wang, Hanchen Liu, Yijuan Ye, Wenting Fang, Anlan Lin, Xiaoman Dai, Qinyong Ye, Xiaochun Chen, Jing Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Aging · 2025
    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

9 authors.

Yu Wang *Department of Neurology, Fujian Key Laboratory of Molecular Neurology and Institute of Neuroscience, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
Hanchen Liu *Department of Neurology, Fujian Key Laboratory of Molecular Neurology and Institute of Neuroscience, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
Yijuan YeDepartment of Neurology, Fujian Key Laboratory of Molecular Neurology and Institute of Neuroscience, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
Wenting FangDepartment of Neurology, Fujian Key Laboratory of Molecular Neurology and Institute of Neuroscience, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
Anlan LinDepartment of Neurology, Fujian Key Laboratory of Molecular Neurology and Institute of Neuroscience, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
Xiaoman DaiDepartment of Neurology, Fujian Key Laboratory of Molecular Neurology and Institute of Neuroscience, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
Qinyong YeDepartment of Neurology, Fujian Key Laboratory of Molecular Neurology and Institute of Neuroscience, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China.
Xiaochun ChenDepartment of Neurology, Fujian Key Laboratory of Molecular Neurology and Institute of Neuroscience, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China. chenxc998@fjmu.edu.cn.
Jing ZhangDepartment of Neurology, Fujian Key Laboratory of Molecular Neurology and Institute of Neuroscience, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, China. drzj@fjmu.edu.cn.

Funding

National Science and Technology Innovation 2030 Major Projects 2022ZD0211600National Science Foundation of China U21A20362
6 · The paper itself

Abstract

Apolipoprotein E (APOE) has garnered significant attention as one of the most influential genetic risk factors for Alzheimer's disease (AD). While the pathogenic role of APOE4 in sporadic AD has been extensively studied, research on the protective effects of the APOE2 genotype and its underlying mechanisms remains limited. Additionally, the existence of sex differences in the protective effects of ApoE2 continues to be a topic of debate. In this study, we utilized humanized ApoE2- and ApoE3- target replacement mice to examine the sex-specific effects of ApoE2 on cognition. Compared with female ApoE3 mice, we found significantly lower spatial cognitive ability and impaired hippocampal synaptic ultrastructure in aged female ApoE2 mice, accompanied by reduced insulin signaling of the hippocampus. Further analyses by target metabolomics and transcriptomic analyses revealed that female ApoE2 mice exhibit an age-related decline in hippocampal inositol levels, and that alterations in inositol levels lower insulin signaling. Importantly, inositol supplementation was found to alleviate peripheral glucose intolerance, enhance insulin signaling, and ultimately improve cognitive function. Interestingly, these differences were not observed between male ApoE2 and ApoE3 mice. The research findings not only provide new insights into the impact of ApoE2 on cognition but also offer a new strategy for cognitive improvement through inositol supplementation in older women.

Indexed as

AgingApolipoprotein E2CognitionHippocampusInsulinSex CharacteristicsSignal TransductionAnimalsApolipoprotein E3FemaleInositolMaleMiceMice, Inbred C57BLApolipoprotein E2Apolipoprotein E3InositolInsulinAlzheimer's diseaseApoEInositolInsulin signalingSex differences

Identifiers

PMID40011916
PMCPMC11866816

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.