Evidence map›Paper›PMID 40186694›Full record

ArticleMolecular neurobiology2025

Whole Transcriptome RNA-Seq Reveals Drivers of Pathological Dysfunction in a Transgenic Model of Alzheimer's Disease.

Nikita Potemkin, Sophie M F Cawood, Diane Guévremont, Bruce Mockett, Jackson Treece, Jo-Ann L Stanton, Joanna M Williams

Abstract read
In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

7 authors.

Nikita PotemkinDepartment of Anatomy, School of Biomedical Sciences, University of Otago, P.O. Box 56, Dunedin, New Zealand.
Sophie M F CawoodDepartment of Anatomy, School of Biomedical Sciences, University of Otago, P.O. Box 56, Dunedin, New Zealand.
Diane GuévremontDepartment of Anatomy, School of Biomedical Sciences, University of Otago, P.O. Box 56, Dunedin, New Zealand.
Bruce MockettBrain Health Research Centre, Brain Research New Zealand-Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
Jackson TreeceDepartment of Anatomy, School of Biomedical Sciences, University of Otago, P.O. Box 56, Dunedin, New Zealand.
Jo-Ann L StantonDepartment of Anatomy, School of Biomedical Sciences, University of Otago, P.O. Box 56, Dunedin, New Zealand.
Joanna M WilliamsDepartment of Anatomy, School of Biomedical Sciences, University of Otago, P.O. Box 56, Dunedin, New Zealand. Joanna.williams@otago.ac.nz.ORCID http://orcid.org/0000-0003-3936-2220

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) affects more than 55 million people worldwide, yet current theories cannot fully explain its aetiology. Accordingly, gene expression profiling has been used to provide a holistic view of the biology underpinning AD. Focusing primarily on protein-coding genes, such approaches have highlighted a critical involvement of microglia-related inflammatory processes. Simultaneous investigation of transcriptional regulators and noncoding RNA (ncRNA) can offer further insight into AD biology and inform the development of disease-modifying therapies. We previously described a method for whole transcriptome sampling to simultaneously investigate protein-coding genes and ncRNA. Here, we use this technique to explore transcriptional changes in a murine model of AD (15-month-old APP/PS1 mice). We confirmed the extensive involvement of microglia-associated genes and gene networks, consistent with literature. We also report a wealth of differentially-expressed non-coding RNA - including microRNA, long non-coding RNA, small nuclear and small nucleolar RNA, and pseudogenes - many of which have been overlooked previously. Transcription factor analysis determined that six transcription factors likely regulate gene expression changes in this model (Irf8, Junb, c-Fos, Lmo2, Runx1, and Nfe2l2). We then utilised validated miRNA-target interactions, finding 60 interactions between 15 miRNA and 42 mRNA (messenger RNA) with largely consistent directionality. Furthermore, we found that eight transcription factors (Clock, Lmo2, Runx1, Nfe2l2, Egr2, c-Fos, Junb, and Nr4a1) are likely responsible for the regulation of miRNA expression. Taken together, these data indicate a complex interplay of coding and non-coding RNA, driven by a small number of specific transcription factors, contributing to transcriptional changes in 15-month-old APP/PS1 mice.

Indexed as

Alzheimer DiseaseRNA-SeqTranscriptomeAnimalsDisease Models, AnimalGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksMiceMice, TransgenicMicrogliaRNA, UntranslatedTranscription FactorsRNA, UntranslatedTranscription FactorsAlzheimer’s diseaseAPP/PS1BioinformaticsNoncoding-RNARNA-Seq

Identifiers

PMID40186694
PMCPMC12289781

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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.