Evidence map›Paper›PMID 40258814›Full record

ArticleCell death discovery2025

APOE4 impairs macrophage lipophagy and promotes demyelination of spiral ganglion neurons in mouse cochleae.

Junru Chen, Haibing Chen, Qinjun Wei, Yajie Lu, Tianming Wang, Xiuhong Pang, Guangqian Xing, Zhibin Chen, Xin Cao, Jun Yao

Abstract read
In one paragraph

Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
–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

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Lipophagy and lipid droplets in neurodegeneration.Trends in pharmacological sciences · 2026
    Review
  3. Article
  4. Article
  5. Autophagy in Sensorineural Hearing Loss: Jekyll or Hyde?International journal of molecular sciences · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. 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

10 authors.

Junru ChenDepartment of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
Haibing ChenDepartment of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
Qinjun WeiDepartment of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
Yajie LuDepartment of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
Tianming WangCentral Laboratory, Translational Medicine Research Center, the affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China.ORCID http://orcid.org/0000-0003-2611-9483
Xiuhong PangDepartment of Otolaryngology-Head and Neck Surgery, the Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, China.
Guangqian XingDepartment of Otolaryngology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Zhibin ChenDepartment of Otolaryngology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China. czbnj@163.com.
Xin CaoDepartment of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, China. caoxin@njmu.edu.cn.ORCID http://orcid.org/0000-0002-8211-6634
Jun YaoDepartment of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, China. joelyao@njmu.edu.cn.ORCID http://orcid.org/0000-0001-7993-6714

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32070587National Natural Science Foundation of China (National Science Foundation of China) 82071052National Natural Science Foundation of China (National Science Foundation of China) 82200642
6 · The paper itself

Abstract

The ApoE-ε4 gene is a well-established genetic risk factor for neurodegenerative diseases, such as Alzheimer's disease and multiple sclerosis, which are characterized by axonal demyelination in the central nervous system. Recent studies have implicated ApoE-ε4 in age-related hearing loss (ARHL), suggesting a potential role of APOE4 isoform in peripheral nervous system degeneration. However, the role of APOE4 in ARHL are still unclear. In this study, we explored the potential role of APOE4 in axonal demyelination of spiral ganglion neurons (SGNs). ApoE-ε4/ε4 (APOE4) and ApoE-ε3/ε3 (APOE3) mice were used to characterize SGNs. The effect of APOE4 on phagocytosis and autophagy as well as intracellular cholesterol level was evaluated in resident cochlear macrophages (RCMs) and mouse bone marrow-derived macrophages (BMDMs). The results showed that significant axonal demyelination was observed in SGNs of 10-month-old APOE4 mice, accompanied by the presence of myelin debris engulfed by RCMs. Meanwhile, inhibited phagocytosis of myelin debris and impaired lipophagy were detected in APOE4 RCMs and APOE4 BMDMs with an aberrant accumulation of lipid droplets (LDs), which could be reversed by trehalose treatment. This study provided a deep insight into the pathogenesis of APOE4-induced axonal demyelination of SGNs associated with the impaired lipophagy in RCMs, which helped to elucidate the underlying mechanism of ApoE-ε4 in ARHL.

Identifiers

PMID40258814
PMCPMC12012174

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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.