Evidence map›Paper›PMID 42147196›Full record

ArticleResearch square2026

Sex-specific immune-brain coupling in hippocampal circuits and Alzheimer's disease vulnerability.

Dana M Parker, Emily Yi, Whitney Tang, Alison Bamford, Lisa Taylor, Scotty Simmons, Novelle Meza, Nandita Tuteja, Brenda Avila, Evelyn Chang and 7 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

17 authors.

Dana M ParkerCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.ORCID 0000-0002-9822-412X
Emily YiCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.
Whitney TangCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.
Alison BamfordInstitute for Interdisciplinary Salivary Bioscience Research, University of California Irvine.
Lisa TaylorCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.
Scotty SimmonsCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.
Novelle MezaCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.
Nandita TutejaCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.
Brenda AvilaCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.
Evelyn ChangCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.
Jason R BockCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.
Liv McMillanCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.
Soyun KimCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.
Jenna N AdamsCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.ORCID 0000-0002-6702-3851
Elizabeth A ThomasDepartment of Neurobiology and Behavior, University of California Irvine, CA, USA.
Emily G JacobsDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, CA, USA.
Michael A YassaCenter for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.ORCID 0000-0002-8635-1498

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Women face twice the lifetime risk of Alzheimer's disease (AD) compared with men. Inflammatory burden is widely implicated in AD, but whether sex-differentiated vulnerability is determined by cytokine levels or by the brain's sensitivity to those signals remains unclear. Here, we examined sex-specific associations between peripheral inflammatory markers, medial temporal lobe (MTL) white matter microstructure using NODDI diffusion MRI, and hippocampal-dependent memory in 121 cognitively unimpaired older adults. Women exhibited widespread alterations in MTL white matter microstructure relative to men. In women, peripheral cytokines (TNFα, IL-10) were associated with microstructural variation in hippocampal-prefrontal tracts, whereas these associations were absent in men. An indirect association between TNFα and memory through hippocampal cingulum neurite density was observed only in women. Despite these microstructural and coupling differences, cytokine levels were comparable between sexes, indicating that risk may be better captured by the coupling between peripheral immune signals and circuit integrity than by cytokine levels alone. These findings identify a sex-specific pattern of immune-brain coupling that reframes inflammatory risk in AD as a property of circuit-level sensitivity rather than overall inflammatory burden.

Indexed as

cytokinesdiffusion MRIhippocampal circuitrymnemonic discriminationNeuroinflammationNODDIsex differenceswhite matter

Identifiers

PMID42147196
PMCPMC13174779

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.