Evidence map›Paper›PMID 40578769›Full record

ArticleNeurobiology of disease2025

Interneuron transcriptomics reveals pathologic markers of Alzheimer's disease progression.

Kevin S Chen, Mohamed H Noureldein, Diana M Rigan, John M Hayes, Kyle J Loi, Junguk Hur, Masha G Savelieff, Eva L Feldman

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Extracellular Vesicles in Tauopathies: Mechanisms and Applications.International journal of molecular sciences · 2026
    Review
  5. Frontiers in artificial intelligence · 2026
    Article
  6. Review
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Kevin S ChenDepartment of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Neurosurgery, University of Michigan, Ann Arbor, MI, 48109, USA; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: kechen@med.umich.edu.
Mohamed H NoureldeinDepartment of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: mnoureld@med.umich.edu.
Diana M RiganDepartment of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: drigan@med.umich.edu.
John M HayesDepartment of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: jmhayes@med.umich.edu.
Kyle J LoiDepartment of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: kloi@med.umich.edu.
Junguk HurDepartment of Biomedical Sciences, University of North Dakota, Grand Forks, ND, 58202, USA. Electronic address: junguk.hur@med.und.edu.
Masha G SavelieffDepartment of Biomedical Sciences, University of North Dakota, Grand Forks, ND, 58202, USA. Electronic address: masha.savelieff@ndus.edu.
Eva L FeldmanDepartment of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Neurosurgery, University of Michigan, Ann Arbor, MI, 48109, USA; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: efeldman@umich.edu.

Funding

Neural Stem Cell Transplantation: A Novel Cellular Therapy for Alzheimer's DiseaseU01AG057562 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FELDMAN, EVA LUCILLE, MURPHY, GEOFFREY G · 2018 to 2020
$3.5M
Mapping and modeling inhibitory interneurons in Alzheimer's disease and related dementias: novel strategies to reverse neural network dysfunctionK08AG084902 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Kevin Showen Chen · 2024 to 2026
$507k
Metabolic syndrome impairs oligodendrocyte metabolic support of neurons leading to Alzheimer’s disease/Alzheimer’s disease and related dementiasK99AG081390 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NOURELDEIN, MOHAMED HUSSEIN MOHAMED · 2023 to 2024
$211k
NIA NIH HHS K08 AG084902NIA NIH HHS K99 AG081390NIA NIH HHS U01 AG057562
6 · The paper itself

Abstract

Alzheimer's disease (AD) exhibits imbalance between neuronal excitation and inhibition, likely secondary to interneuron dysfunction. To reveal underlying mediators, we spatially profiled the transcriptome of neuronal subtypes in 5XFAD versus control mice at early- and late-stage disease. Pooled analysis of neuron types showed expected pathways at early-stage (RNA and protein processing pathways) versus late-stage (neurodegenerative pathways) disease. Early-stage interneurons exhibited alterations in AD-related RNA and protein pathways along with canonical neurodegenerative pathways. Early-stage excitatory neurons, however, showed changes in axon guidance and synapse pathways, without representation of neurodegenerative pathways. Classical neurodegenerative pathways were represented only in late-stage excitatory neurons. Late-stage interneurons instead featured neuronal and synapse pathways along with cellular, cancer, and infection pathways. Our results suggest earlier neurodegenerative pathway involvement in interneurons, represented in excitatory neurons only at later stages, possibly indicating earlier inhibitory neuron involvement. These transcriptomic profiles offer insight into potential AD pathophysiology and therapeutic targets.

Indexed as

Alzheimer DiseaseInterneuronsTranscriptomeAnimalsDisease ProgressionHumansMaleMiceMice, Transgenic5XFADExcitatoryHyperexcitabilityInhibitoryMouseSpatial transcriptomics

Identifiers

PMID40578769
PMCPMC12931098

What OpenQuestion holds

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Registered trials

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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.