Evidence map›Paper›PMID 40305608›Full record

ArticleScience advances2025

Impaired parvalbumin interneurons in the retrosplenial cortex as the cause of sex-dependent vulnerability in Alzheimer's disease.

Dylan J Terstege, Yi Ren, Bo Young Ahn, Heewon Seo, Kabirat Adigun, Alzheimer’s Disease Neuroimaging Initiative, Liisa A M Galea, Derya Sargin, Jonathan R Epp

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Review
  2. Article
  3. Genetic alterations in SUPT6H are associated with neurodevelopmental disorders.Biochimica et biophysica acta. Molecular basis of disease · 2026
    Article
  4. Article
  5. Reciprocal molecular and cellular cholinergic working memory impairments in Alzheimer's disease model mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Environmental Enrichment Preserves Retrosplenial Parvalbumin Density and Cognitive Function in Female 5xFAD Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  10. 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

9 authors.

Dylan J TerstegeDepartment of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.ORCID 0000-0002-5903-0875
Yi RenDepartment of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Bo Young AhnApplied Spatial Omics Centre, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.ORCID 0009-0002-4583-8950
Heewon SeoApplied Spatial Omics Centre, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.ORCID 0000-0001-6218-8609
Kabirat AdigunDepartment of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.ORCID 0000-0002-3217-7455
Alzheimer’s Disease Neuroimaging Initiative
Liisa A M GaleaDepartment of Psychology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.ORCID 0000-0003-2874-9972
Derya SarginHotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.ORCID 0000-0001-8018-4329
Jonathan R EppDepartment of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.ORCID 0000-0002-7968-8973

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease is a debilitating neurodegenerative disorder with no cure and few treatment options. In early stages of Alzheimer's disease, impaired metabolism and functional connectivity of the retrosplenial cortex strongly predict future cognitive impairments. Therefore, understanding Alzheimer's disease-related deficits in the retrosplenial cortex is critical for understanding the origins of cognitive impairment and identifying early treatment targets. Using the 5xFAD mouse model, we discovered early, sex-dependent alterations in parvalbumin-interneuron transcriptomic profiles. This corresponded with impaired parvalbumin-interneuron activity, which was sufficient to induce cognitive impairments and dysregulate retrosplenial functional connectivity. In fMRI scans from patients with mild cognitive impairment and Alzheimer's disease, we observed a similar sex-dependent dysregulation of retrosplenial cortex functional connectivity and, in postmortem tissue from subjects with Alzheimer's disease, a loss of parvalbumin interneurons. Reversal of cognitive deficits by stimulation of parvalbumin interneurons in the retrosplenial cortex suggests that this may serve as a promising therapeutic strategy.

Indexed as

Alzheimer DiseaseCerebral CortexGyrus CinguliInterneuronsParvalbuminsAgedAnimalsCognitive DysfunctionDisease Models, AnimalFemaleHumansMagnetic Resonance ImagingMaleMiceMice, TransgenicSex FactorsParvalbumins

Identifiers

PMID40305608
PMCPMC12042879

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.