Evidence map›Paper›PMID 40634788›Full record

ArticleMolecular neurobiology2025

The Crosstalk Between Sepsis-Associated Encephalopathy and Alzheimer's Disease: Identifying Potential Biomarkers and Therapeutic Targets for Cognition.

Zhitong Wang, Zhiling Zhang, Jing Shi, Rongsheng Zhao

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

4 authors.

Zhitong WangDepartment of Pharmacy, Peking University Third Hospital; Institute for Drug Evaluation, Peking University Health Science Center; Therapeutic Drug Monitoring and Clinical Toxicology Center, Peking University, Beijing, 100191, China.
Zhiling ZhangDepartment of Pharmacy, Peking University Third Hospital; Institute for Drug Evaluation, Peking University Health Science Center; Therapeutic Drug Monitoring and Clinical Toxicology Center, Peking University, Beijing, 100191, China.
Jing ShiDepartment of Pharmacy, Peking University Third Hospital; Institute for Drug Evaluation, Peking University Health Science Center; Therapeutic Drug Monitoring and Clinical Toxicology Center, Peking University, Beijing, 100191, China.
Rongsheng ZhaoDepartment of Pharmacy, Peking University Third Hospital; Institute for Drug Evaluation, Peking University Health Science Center; Therapeutic Drug Monitoring and Clinical Toxicology Center, Peking University, Beijing, 100191, China. zhaorongsheng@bjmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Patients with sepsis are at a heightened risk of long-term cognitive impairment, including neurodegenerative diseases; however, the underlying pathophysiological mechanisms remain incompletely understood. This study examines key genes associated with sepsis and Alzheimer's disease (AD), as well as their potential molecular mechanisms. We downloaded the GSE135838 dataset from the Gene Expression Omnibus (GEO) database and performed comparative analysis of differentially expressed genes (DEGs) using the AlzData database to identify co-expressed DEGs. Functional and protein-protein interaction (PPI) network analyses were used to identify hub genes and their associated molecular mechanisms. Animal experiments were conducted to validate the role of the central gene C5aR1 in the pathological processes of sepsis-related cognitive impairment, blood-brain barrier (BBB) disruption, and microglial activation. Co-culture experiments were performed to assess the protective effect of C5aR1 against inflammation-induced neuronal damage. In GSE135838, 25 DEGs exhibited consistent expression changes in the brain tissue of AD patients. Notably, LYZ, C5AR1, ZFP36, MPZL2, APOL4, CD163, SERPINA3, and CCL2 showed significant differential expression in the cortex and hippocampus of AD patients. KEGG pathway enrichment analysis revealed that among the 14 pathways meeting the criteria, the TNF signaling pathway demonstrated the highest significance. Key intersections of multiple GO enrichment terms included IL-6, ICAM1, CLEC4E, and PCK1. The top ten hub genes identified from the PPI network analysis included IL6, CCL2, ICAM1, CXCL1, CD163, C5AR1, SOCS3, CLEC4E, HSPB1, and HSPA1A. Pharmacological inhibition of the hub gene product C5aR1 using PMX205 improved cognitive and emotional dysfunction in CLP-induced septic mice and reduced BBB damage and microglial activation. Inhibition of C5aR1 also alleviated microglia-induced neuronal injury. In summary, the neuroimmune dysregulation caused by sepsis is correlated with potential pathological mechanisms in AD. This study provides additional molecular evidence for potential biomarkers and therapeutic targets for drug intervention in the risk of AD among sepsis survivors.

Indexed as

Alzheimer DiseaseBiomarkersCognitionSepsisSepsis-Associated EncephalopathyAnimalsBlood-Brain BarrierGene Regulatory NetworksHumansMiceProtein Interaction MapsReceptor, Anaphylatoxin C5aSignal TransductionBiomarkersReceptor, Anaphylatoxin C5aAlzheimer’s DiseaseC5aR1NeuroinflammationSepsis-Associated Encephalopathy

Identifiers

PMID40634788

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.