Evidence mapPaperPMID 40232249Full record

ArticleJournal of Alzheimer's disease : JAD2025

Alzheimer's disease as an auto-innate immune pathology with potential cell trans-differentiation and enhanced trained immunity in 3xTg-AD mouse model.

Fatma Saaoud, Lu Liu, Keman Xu, Yifan Lu, Ying Shao, Mohammed Ben Issa, Xiaohua Jiang, Xianwei Wang, Xiaolei Liu, Michael Autieri and 13 more

Abstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. The spleen-brain axis in Alzheimer's disease and related dementias: Integrating immune and metabolic regulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  6. Article
  7. 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

23 authors.

Fatma SaaoudLemole Center for Integrated Lymphatics and Vascular Research, Temple University, Philadelphia, PA, USA.ORCID 0000-0001-5807-3390
Lu LiuLemole Center for Integrated Lymphatics and Vascular Research, Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0009-0006-5973-4086
Keman XuLemole Center for Integrated Lymphatics and Vascular Research, Temple University, Philadelphia, PA, USA.ORCID 0000-0002-0816-1760
Yifan LuLemole Center for Integrated Lymphatics and Vascular Research, Temple University, Philadelphia, PA, USA.ORCID 0000-0003-4461-0698
Ying ShaoLemole Center for Integrated Lymphatics and Vascular Research, Temple University, Philadelphia, PA, USA.ORCID 0000-0001-5879-0154
Mohammed Ben IssaLemole Center for Integrated Lymphatics and Vascular Research, Temple University, Philadelphia, PA, USA.ORCID 0009-0009-5928-6617
Xiaohua JiangLemole Center for Integrated Lymphatics and Vascular Research, Temple University, Philadelphia, PA, USA.ORCID 0000-0003-3325-6531
Xianwei WangLemole Center for Integrated Lymphatics and Vascular Research, Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0002-9603-1324
Xiaolei LiuLemole Center for Integrated Lymphatics and Vascular Research, Temple University, Philadelphia, PA, USA.ORCID 0000-0002-6881-3716
Michael AutieriLemole Center for Integrated Lymphatics and Vascular Research, Temple University, Philadelphia, PA, USA.ORCID 0000-0003-1039-7577
Sheng WuLemole Center for Integrated Lymphatics and Vascular Research, Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0003-2944-0475
Juncheng WeiLemole Center for Integrated Lymphatics and Vascular Research, Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0002-1858-6121
Jun YuLemole Center for Integrated Lymphatics and Vascular Research, Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0003-4530-2179
Rihab BoucharebLemole Center for Integrated Lymphatics and Vascular Research, Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0002-6468-1269
Avrum GillespieSection of Nephrology, Hypertension, and Kidney Transplantation, Department of Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0002-7528-5800
Jin Jun LuoDepartment of Neurology, Temple University, Philadelphia, PA, USA.ORCID 0000-0001-9883-0763
Laisel MartinezDeWitt Daughtry Family Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA.ORCID 0000-0002-3009-8761
Roberto Vazquez-PadronDeWitt Daughtry Family Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA.ORCID 0000-0002-9370-276X
Jianxin SunDepartment of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0001-5319-912X
Huaqing ZhaoDepartment of Biomedical Education and Data Sciences, Temple University, Philadelphia, PA, USA.ORCID 0000-0002-0953-4768
Hong WangLemole Center for Integrated Lymphatics and Vascular Research, Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0001-6258-4070
Domenico PraticoAlzheimer's Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0002-8347-613X
Xiaofeng YangLemole Center for Integrated Lymphatics and Vascular Research, Temple University, Philadelphia, PA, USA.ORCID 0000-0002-6854-6195

Funding

LysoPI/GPR55 pathway promotes endothelial activation, vascular inflammation and atherosclerosisR01HL163570 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · 2024 to 2025
$1.3M
Dissecting the functional roles of cardiac lymphatics in ischemic heart diseaseR01HL163269 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · 2024 to 2025
$931k
Platelet-mitochondria transplantation to treat mitochondrial dysfunction in acute kidney injuryR01DK135470 · TEMPLE UNIV OF THE COMMONWEALTH · 2025 to 2025
$311k
NHLBI NIH HHS R01 HL147565NHLBI NIH HHS R01 HL153599NHLBI NIH HHS R01 HL163269NHLBI NIH HHS R01 HL163570NIDDK NIH HHS R01 DK113775NIDDK NIH HHS R01 DK135470
6 · The paper itself

Abstract

BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder characterized by memory impairment. Neuroinflammatory processes, mediated by glial and immune cells, contribute to neuronal damage. Emerging evidence implicates innate immune mechanisms, including trained immunity and cell trans-differentiation, in AD pathogenesis, though their roles remain unclear.ObjectiveTo investigate transcriptomic changes in the 3xTg-AD mouse model, focusing on trained immunity and cell trans-differentiation in disease mechanisms.MethodsRNA-sequencing was performed on brain tissue (cortex plus hippocampus) from 11-month-old female 3xTg-AD and wild-type mice (n = 3/group). Differentially expressed genes (fold change > 1.5, p < 0.05) were identified and followed by bioinformatics and knowledge-based transcriptomic profiling. Public AD datasets were also analyzed.Results3xTg-AD mice exhibited 316 upregulated and 412 downregulated genes. Downregulated genes included those for blood-brain barrier protein, while upregulated genes related to cerebrospinal fluid. Increased expression of proinflammatory markers, as well as genes related to cell differentiation, proliferation, activation, and adhesion. Upregulation of genes associated with cell migration and trans-differentiation suggests a potential role for inflammation and cellular plasticity. Additionally, genes involved in inflammasome pathways, immunometabolism, and trained immunity were upregulated. Mechanistically, these genes were modulated by knockdown of trained immunity promoter SET-7, overexpression of trained immunity inhibitor IL-37, and knockout of inflammasome genes IL-1 receptor, caspase-1, and pattern recognition receptor CD36.ConclusionsThe finding underscore the potential role of trained immunity and cell trans-differentiation in AD, revealing a mechanistic framework in which danger-associated molecular patterns drive innate immune responses, inflammasome activation, and cell plasticity contribute to AD, offering therapeutic targets for neuroinflammation and cellular reprograming.

Indexed as

Alzheimer DiseaseCell TransdifferentiationImmunity, InnateAnimalsBrainDisease Models, AnimalFemaleMiceMice, TransgenicTrained ImmunityTranscriptomeAlzheimer's diseaseamyloid-βblood-brain barriercell trans-differentiationtrained immunity

Identifiers

PMID40232249
PMCPMC12288048

What Socratic holds

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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.