Evidence map›Paper›PMID 41895266›Full record

ArticleNeuron2026

Sex-specific APOE4-dependent innate immunity regulates meningeal lymphatics, brain lipids, neuroinflammation, and cognition.

Nickoleta Delivanoglou, Kennedi T Todd, Francisco Almeida, Shanon Rego, Amogh Changavi, Myriam Spajer, Virginia Estades Ayuso, Liliana M Pinho-Correia, Guadalupe Sanchez, Sofia P das Neves and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

22 authors.

Nickoleta DelivanoglouDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Kennedi T ToddCenter for Accelerated Nanotherapeutics, Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
Francisco AlmeidaLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Shanon RegoDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Neuroscience PhD Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL 32224, USA.
Amogh ChangaviHerbert Wertheim School of Optometry & Vision Science Bioinformatics Core, University of California, Berkeley, Berkeley, CA, USA.
Myriam SpajerParis Brain Institute, Université Pierre et Marie Curie Paris 06 UMRS1127, Sorbonne Université, Paris Brain Institute, Paris, France.
Virginia Estades AyusoDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Neuroscience PhD Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL 32224, USA.
Liliana M Pinho-CorreiaDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Guadalupe SanchezDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Neuroscience PhD Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL 32224, USA.
Sofia P das NevesDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Megan J BarberDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Racquelle SchraderDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Post-baccalaureate Research Education Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL 32224, USA.
Patricia SacilottoDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Yuka A MartensDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Michael G HeckmanDivision of Clinical Trials and Biostatistics, Mayo Clinic, Jacksonville, FL 32224, USA.
Guojun BuDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Rudolph E TanziMcCance Center for Brain Health and Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02145, USA.
Jean-Leon ThomasParis Brain Institute, Université Pierre et Marie Curie Paris 06 UMRS1127, Sorbonne Université, Paris Brain Institute, Paris, France; Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
John D FryerCenter for Accelerated Nanotherapeutics, Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
Tiago Gil OliveiraLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal; Department of Neuroradiology, ULS/Hospital de Braga, 4710-243 Braga, Portugal.
Karthik ShekharDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA; Helen Wills Neuroscience Institute, Vision Sciences Graduate Program, Center for Computational Biology, Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA, USA.
Sandro Da MesquitaDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Neuroscience PhD Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL 32224, USA. Electronic address: damesquita@mayo.edu.

Funding

Research Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI KEJAL KANTARCI · 2019 to 2026
$33.5M
Role of apoE-mediated meningeal lymphatic remodeling in the pathophysiology of Alzheimer’s diseaseRF1AG080556 · NIA · MAYO CLINIC JACKSONVILLE · PI DA MESQUITA, SANDRO · 2023 to 2023
$2.3M
Role of meningeal lymphatic vasculature in neuroimmune communication developmentR01NS130057 · NINDS · YALE UNIVERSITY · PI Anne Christine Eichmann, AKIKO IWASAKI · 2023 to 2026
$2.1M
NIA NIH HHS P30 AG062677NIA NIH HHS RF1 AG080556NINDS NIH HHS R01 NS130057
6 · The paper itself

Abstract

Sex and apolipoprotein E ε4 (APOE4) interact to alter the risk for Alzheimer's disease and other neurodegenerative disorders. Herein, we show sex-specific differences in immune activation and lymphatic function in the meningeal dura of humanized female and male mice expressing two alleles of APOE4 (E4/E4), when compared with their respective sex-matched E3/E3 controls. We also describe distinct effects of APOE4 on brain lipid composition and inflammation in females and males that were partially reverted upon colony-stimulating factor 1 receptor (CSF1R) inhibition. Suppressing innate immunity reduced neuroinflammation and restored cognitive function in E4/E4 females, while exacerbating neuroinflammation and accelerating cognitive decline in E4/E4 males. Finally, in line with the E4/E4 humanized mouse model data, we show that APOE4 expression is linked to sexually dimorphic leukocyte activation profiles in the human brain. This study highlights the need for personalized therapies when targeting APOE, brain immunity, and meningeal lymphatics to promote cognitive resilience in both females and males.

Indexed as

Apolipoprotein E4BrainCognitionHistocompatibility Antigens Class IIMacrophagesAdaptive ImmunityAlzheimer DiseaseAnimalsCase-Control StudiesCytokinesDatasets as TopicDura MaterFemaleHeterozygoteHumansImmunity, InnateApolipoprotein E4Csf1r protein, mouseCytokinesHistocompatibility Antigens Class IIReceptors, Granulocyte-Macrophage Colony-Stimulating FactorAPOE4brain lipidscognitionCSF1R inhibitorhuman brain leukocyteslymphatic drainagemacrophagesmeningesneuroinflammationsexual dimorphism

Identifiers

PMID41895266
PMCPMC13035321

What OpenQuestion 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 OpenQuestion graph.