Evidence map›Paper›PMID 40865635›Full record

ArticleJournal of advanced research2026

Spatial-temporal lipidomics reveals dysregulated lipid metabolism in mouse brain during Alzheimer's disease progression.

Hongli Li, Zhihao Zhao, Lemei Zhu, Yejun Tan, Zheyu Zhang, Zhen Zhang, Jin Kang, Hongmei Lu, Weijun Peng, Qian Wu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. ExploringFrontiers in cell and developmental biology · 2026
    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.

Hongli LiDepartment of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; National Clinical Research Center for Mental Disorder, Changsha, Hunan 410011, China.
Zhihao ZhaoCollege of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, China.
Lemei ZhuDepartment of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Academician Workstation of Changsha Medical University, Changsha, Hunan 410219, China.
Yejun TanSchool of Mathematics, University of Minnesota Twin Cities, Minneapolis, MN 55455, United States.
Zheyu ZhangDepartment of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; National Clinical Research Center for Mental Disorder, Changsha, Hunan 410011, China.
Zhen ZhangYangSheng College of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, China.
Jin KangDepartment of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
Hongmei LuCollege of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, China.
Weijun PengDepartment of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; National Clinical Research Center for Mental Disorder, Changsha, Hunan 410011, China. Electronic address: pengweijun87@csu.edu.cn.
Qian WuCollege of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, China. Electronic address: qianwu@csu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionTracking spatial lipidomic changes during Alzheimer's disease (AD) progression is crucial for elucidating the underlying mechanisms of the disease.

objectivesThis study aims to investigate the spatial-temporal lipidomic alterations and their associated metabolic enzyme changes during AD progression.

methodsThe spatial lipidomic changes and corresponding alterations in metabolic enzymes during AD progression in amyloid precursor protein/presenilin-1 (APP/PS1) mice were thoroughly analyzed using an advanced ambient mass spectrometry imaging (MSI) technique, complemented by immunofluorescence (IF) imaging.

resultsDistinct lipidomic differences were observed between AD and wild-type (WT) mice in both the hippocampus (HP) and thalamus (TH), with the TH region exhibiting more significant lipid changes than the HP. A total of 88 lipid species with age- and region-specific alterations were identified, primarily within the sphingolipid, glycerolipid, and glycerophospholipid metabolic pathways. These metabolic changes were corroborated by IF imaging, which demonstrated spatial variations in the corresponding enzymes within the lipid metabolic pathways. Notably, a significant downregulation of hexosylceramides (HexCers) in the white matter of aged APP/PS1 mice suggests potential white matter abnormalities linked to AD. Correlation analysis further revealed that reduced HexCers were associated with the inhibited sulfatide-HexCer pathway, potentially driven by diminished ARSA levels, a factor known to be involved in microglial activation and inflammation. Additionally, upregulation of diacylglycerol (DG), observed even during the pre-symptomatic phase of AD, suggests DG as an early diagnostic biomarker. A strong correlation between the spatial changes in the DG-to-phosphatidylcholine (PC) ratio and phospholipase C (PLC) expression indicates that DG upregulation may result from PLC activation, a process known to be induced by amyloid β.

conclusionsThis study provides an expanded spatial, temporal, and chemical perspective on AD mechanisms, offering potential avenues for enhancing early diagnosis and therapeutic strategies.

Indexed as

Alzheimer DiseaseBrainLipid MetabolismLipidomicsAmyloid beta-Protein PrecursorAnimalsDisease Models, AnimalDisease ProgressionHippocampusMaleMiceMice, TransgenicPresenilin-1Amyloid beta-Protein PrecursorPresenilin-1Alzheimer’s diseaseAmbient mass spectrometry imagingGlycerolipid & glycerophospholipid metabolismSpatial lipidomicsSphingolipid metabolism

Identifiers

PMID40865635
PMCPMC13131509

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.