Evidence map›Paper›PMID 40738263›Full record

ArticleBrain, behavior, and immunity2025

Genotype and microbiome shape immunity in a sex-specific manner in mouse models of Alzheimer's disease.

John W Bostick, T Jaymie Connerly, Taren Thron, Brittany D Needham, Matheus de Castro Fonseca, Rima Kaddurah-Daouk, Rob Knight, Sarkis K Mazmanian

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain, behavior, and immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Frontiers in pharmacology · 2026
    Article
  5. Exploring the relationship betweenFrontiers in neuroscience · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

John W BostickDivision of Biology and Biological Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena, CA 91125, USA. Electronic address: jwbostick@ufl.edu.
T Jaymie ConnerlyDivision of Biology and Biological Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena, CA 91125, USA.
Taren ThronDivision of Biology and Biological Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena, CA 91125, USA.
Brittany D NeedhamDivision of Biology and Biological Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena, CA 91125, USA; Duke Institute of Brain Sciences, Duke University, 308 Research Dr, Durham, NC 27710, USA.
Matheus de Castro FonsecaDivision of Biology and Biological Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena, CA 91125, USA.
Rima Kaddurah-DaoukDepartment of Psychiatry and Behavioral Sciences, Duke University, 905 W Main St, Durham, NC 27701, USA; Duke Institute of Brain Sciences, Duke University, 308 Research Dr, Durham, NC 27710, USA; Department of Medicine, Duke University, 40 Duke Medicine Cir Rm 401, Davison Bldg, Durham, NC 27710, USA.
Rob KnightDepartment of Pediatrics, University of California San Diego, 9461 Gilman Dr, La Jolla, CA 92093, USA; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, 9500 Gilman Dr, MC 0412, La Jolla, CA 92093, USA; Department of Computer Science & Engineering, University of California San Diego, 9500 Gilman Dr, MC 0404, La Jolla, CA 92093, USA; Halicioğlu Data Science Institute, University of California San Diego, 3234 Matthews Ln, La Jolla, CA 92093, USA.
Sarkis K MazmanianDivision of Biology and Biological Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena, CA 91125, USA. Electronic address: sarkis@caltech.edu.

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
Project 4 - Mechanistic studies on the role of the gut microbiome in models for Alzheimer's diseaseU19AG063744 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Rima F Kaddurah-Daouk · 2019 to 2026
$54.1M
Metabolomic Signatures for Disease Sub-classification and Target Prioritization in AMP-ADU01AG061359 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KASTENMULLER, GABI · 2018 to 2022
$10.0M
Metabolic Signatures Underlying Vascular Risk Factors for Alzheimer-type DementiasRF1AG051550 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KLING, MITCHEL ALLAN · 2015 to 2016
$6.3M
Metabolic Networks and Pathways Predictive of Sex Differences in AD Risk and Responsiveness to TreatmentRF1AG059093 · NIA · DUKE UNIVERSITY · PI BRINTON, ROBERTA EILEEN, CHANG, RUI · 2018 to 2018
$5.9M
Metabolic Networks and Pathways in Alzheimer's DiseaseR01AG046171 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F · 2014 to 2017
$4.4M
Gut Liver Brain Biochemical Axis in Alzheimer's DiseaseRF1AG058942 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, VAN DUIJN, CORNELIA MARJA · 2018 to 2018
$3.4M
NIA NIH HHS R01 AG046171NIA NIH HHS RF1 AG051550NIA NIH HHS RF1 AG058942NIA NIH HHS RF1 AG059093NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG061359NIA NIH HHS U19 AG063744
6 · The paper itself

Abstract

Preclinical studies have revealed that the microbiome broadly affects immune responses and deposition and/or clearance of amyloid-beta (Aβ) in mouse models of Alzheimer's disease (AD), but whether, and how, the microbiome shapes central and peripheral immune profiles in AD models remains unknown. We examined adaptive immune responses in two mouse models containing AD-related genetic predispositions (3xTg and 5xFAD) in the presence or absence of the microbiome to determine if it promotes dysregulated immune responses and cognition in AD. T and B cells were altered in central nervous system (CNS)-associated lymph nodes and systemic immune tissues between genetic models and wildtype mice, with earlier signs of heightened immune activity in females. Systemic immune responses were modulated by the microbiome and differed by sex. Further, the absence of a microbiome in germ-free mice resulted in increased cognitive deficits, primarily in males. These data reveal sexual dimorphism in early signs of immune activity and microbiome effects, and highlight how sex and the microbiome shape responses in mouse models of AD.

Indexed as

Alzheimer DiseaseMicrobiotaAmyloid beta-PeptidesAnimalsB-LymphocytesDisease Models, AnimalFemaleGastrointestinal MicrobiomeGenotypeMaleMiceMice, Inbred C57BLMice, TransgenicSex CharacteristicsSex FactorsT-LymphocytesAmyloid beta-Peptides3xTg5xFADAdaptive immunityAlzheimer’s diseaseAnimal modelsGerm-freeInflammationMiceMicrobiomeSex-specific

Identifiers

PMID40738263
PMCPMC12490345

What Socratic holds

Textmetadata
LicenceCC BY
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.