Evidence map›Paper›PMID 39755746›Full record

ArticleCommunications biology2025

Reversal of neuronal tau pathology via adiponectin receptor activation.

Eric R McGregor, Danny J Lasky, Olivia J Rippentrop, Josef P Clark, Samantha Wright, Mathew V Jones, Rozalyn M Anderson

Abstract read
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Eric R McGregorDivision of Geriatrics, Department of Medicine, SMPH, University of Wisconsin-Madison, Madison, WI, USA.
Danny J LaskyDepartment of Neuroscience, University of Wisconsin-Madison, Madison, WI, USA.
Olivia J RippentropDepartment of Neuroscience, University of Wisconsin-Madison, Madison, WI, USA.
Josef P ClarkDivision of Geriatrics, Department of Medicine, SMPH, University of Wisconsin-Madison, Madison, WI, USA.
Samantha WrightDepartment of Neuroscience, University of Wisconsin-Madison, Madison, WI, USA.
Mathew V JonesDepartment of Neuroscience, University of Wisconsin-Madison, Madison, WI, USA.
Rozalyn M AndersonDivision of Geriatrics, Department of Medicine, SMPH, University of Wisconsin-Madison, Madison, WI, USA. rozalyn.anderson@wisc.edu.ORCID http://orcid.org/0000-0002-0864-7998

Funding

TRAINING IN NUTRITIONT32DK007665 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI GUY E GROBLEWSKI, Chi- Liang Eric Yen · 1993 to 2026
$9.2M
Acetyl-CoA flux and mitochondrial adaptation: a pathogenic role in aging and AD?RF1AG057408 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI ANDERSON, ROZALYN M., PUGLIELLI, LUIGI · 2017 to 2017
$3.5M
Metabolism of Alzheimer’s Disease: systems and cellular networksR01AG067330 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI ANDERSON, ROZALYN M. · 2020 to 2024
$3.4M
Molecular Networks in Aging and Caloric Restriction in Rhesus MonkeysR01AG074503 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Rozalyn M. Anderson · 2022 to 2026
$3.1M
Learning, Memory, and Plasticity (LaMP) Training ProgramT32MH112507 · NIMH · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Karen Zito · 2017 to 2026
$2.4M
BLRD VA I01 BX003846NIA NIH HHS R01 AG067330NIA NIH HHS R01 AG074503NIA NIH HHS RF1 AG057408NIDDK NIH HHS T32 DK007665NIMH NIH HHS T32 MH112507U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) T32DK007665U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG057408U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG067330
6 · The paper itself

Abstract

Changes in brain mitochondrial metabolism are coincident with functional decline; however, direct links between the two have not been established. Here, we show that mitochondrial targeting via the adiponectin receptor activator AdipoRon (AR) clears neurofibrillary tangles (NFTs) and rescues neuronal tauopathy-associated defects. AR reduced levels of phospho-tau and lowered NFT burden by a mechanism involving the energy-sensing kinase AMPK and the growth-sensing kinase GSK3b. The transcriptional response to AR included broad metabolic and functional pathways. Induction of lysosomal pathways involved activation of LC3 and p62, and restoration of neuronal outgrowth required the stress-responsive kinase JNK. Negative consequences of NFTs on mitochondrial activity, ATP production, and lipid stores were corrected. Defects in electrophysiological measures (e.g., resting potential, resistance, spiking profiles) were also corrected. These findings reveal a network linking mitochondrial function, cellular maintenance processes, and electrical aspects of neuronal function that can be targeted via adiponectin receptor activation.

Indexed as

MitochondriaNeuronsReceptors, Adiponectintau ProteinsAnimalsHumansMaleMiceMice, Inbred C57BLNeurofibrillary TanglesPiperidinesTauopathiesAdipoRonPiperidinesReceptors, Adiponectintau Proteins

Identifiers

PMID39755746
PMCPMC11700159

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.