Evidence map›Paper›PMID 39269584›Full record

ArticleGeroScience2025

Activation of the muscle-to-brain axis ameliorates neurocognitive deficits in an Alzheimer's disease mouse model via enhancing neurotrophic and synaptic signaling.

Hash Brown Taha, Allison Birnbaum, Ian Matthews, Karel Aceituno, Jocelyne Leon, Max Thorwald, Jose Godoy-Lugo, Constanza J Cortes

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in GeroScience, 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. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Prosaposin in CNS health and disease, metabolic stress and exercise adaptation.Journal of molecular medicine (Berlin, Germany) · 2026
    Review
  7. Article
  8. Review
  9. 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

8 authors.

Hash Brown TahaLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90007, USA.
Allison BirnbaumDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
Ian MatthewsLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90007, USA.
Karel AceitunoLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90007, USA.
Jocelyne LeonLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90007, USA.
Max ThorwaldLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90007, USA.
Jose Godoy-LugoLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90007, USA.
Constanza J CortesLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90007, USA. cjc_149@usc.edu.

Funding

USC Geroscience Training in the Biology of AgingT32AG052374 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Sean P CURRAN · 2016 to 2026
$5.3M
Exercise-Associated Signaling Against CNS Aging and Alzheimer's DiseaseR01AG077536 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Constanza Javiera Cortes · 2022 to 2026
$2.4M
Alzheimer's Association AARF-21-851362NIA NIH HHS R01 912 AG077536 (NIA NIH HHS R01 AG077536NIA NIH HHS T32 AG052374
6 · The paper itself

Abstract

Skeletal muscle regulates central nervous system (CNS) function and health, activating the muscle-to-brain axis through the secretion of skeletal muscle-originating factors ("myokines") with neuroprotective properties. However, the precise mechanisms underlying these benefits in the context of Alzheimer's disease (AD) remain poorly understood. To investigate muscle-to-brain axis signaling in response to amyloid β (Aβ)-induced toxicity, we generated 5xFAD transgenic female mice with enhanced skeletal muscle function (5xFAD;cTFEB;HSACre) at prodromal (4-months old) and late (8-months old) symptomatic stages. Skeletal muscle TFEB overexpression reduced Aβ plaque accumulation in the cortex and hippocampus at both ages and rescued behavioral neurocognitive deficits in 8-month-old 5xFAD mice. These changes were associated with transcriptional and protein remodeling of neurotrophic signaling and synaptic integrity, partially due to the CNS-targeting myokine prosaposin (PSAP). Our findings implicate the muscle-to-brain axis as a novel neuroprotective pathway against amyloid pathogenesis in AD.

Indexed as

Alzheimer DiseaseBrainMuscle, SkeletalAmyloid beta-PeptidesAnimalsDisease Models, AnimalFemaleMiceMice, TransgenicPlaque, AmyloidSignal TransductionAmyloid beta-PeptidesMuscleMuscle-to-brain axisMyokinesPlaquesSynapse

Identifiers

PMID39269584
PMCPMC11978596

What OpenQuestion holds

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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 OpenQuestion graph.