Evidence map›Paper›PMID 42187024›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Systemic delivery of synapsin-promoted caveolin-1 overexpression ameliorates pathological TDP-43-induced cognitive decline and neurodegenerative changes.

Dongsheng Wang, Vinh Ta, Hongxia Wang, Jerica Ju, Chun Wang, Christine Chehadeh, Albertina Torreblanca-Zanca, Yessenia Magaña, Michael J Castle, Shanshan Wang and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

11 authors.

Dongsheng WangDepartment of Anesthesiology, University of California San Diego, La Jolla, California, USA.
Vinh TaDepartment of Anesthesiology, University of California San Diego, La Jolla, California, USA.
Hongxia WangDepartment of Anesthesiology, University of California San Diego, La Jolla, California, USA.
Jerica JuDepartment of Anesthesiology, University of California San Diego, La Jolla, California, USA.
Chun WangDepartment of Anesthesiology, University of California San Diego, La Jolla, California, USA.
Christine ChehadehDepartment of Anesthesiology, University of California San Diego, La Jolla, California, USA.
Albertina Torreblanca-ZancaDepartment of Neurosciences, University of California San Diego, La Jolla, California, USA.
Yessenia MagañaDepartment of Neurosciences, University of California San Diego, La Jolla, California, USA.
Michael J CastleDepartment of Neurosciences, University of California San Diego, La Jolla, California, USA.
Shanshan WangDepartment of Anesthesiology, University of California San Diego, La Jolla, California, USA.
Brian P HeadDepartment of Anesthesiology, University of California San Diego, La Jolla, California, USA.

Funding

CTSA UM1 Program at University of California San Diego Altman Clinical and Translational Research InstituteUM1TR005449 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael A Hogarth, David Mitchell Smith · 2025 to 2026
$20.6M
UC San Diego Clinical and Translational Research InstituteKL2TR001444 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DEPP, COLIN A. · 2015 to 2024
$15.4M
CTSA K12 Program at University of California San Diego Altman Clinical and Translational Research InstituteK12TR005441 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Colin A. Depp, ADRIANA H TREMOULET · 2025 to 2026
$3.2M
BLRD VA I01 BX003671BLRD VA IK6 BX006318National Institute of healthNCATS NIH HHS K12 TR005441NCATS NIH HHS KL2 TR001444NCATS NIH HHS UM1 TR005449NIH HHS UM1TR005449University of California-San Diego 2039592U.S. Department of Defense AL230115U.S. Department of Veterans Affairs BX006318
6 · The paper itself

Abstract

introductionTransactive response DNA-binding protein 43 (TDP-43) proteinopathy is associated with frontotemporal dementia and Alzheimer's disease (AD). We previously demonstrated that synapsin-promoted caveolin-1 (SynCav1) preserves cognitive function in the mouse model of AD. This study investigated the therapeutic potential of SynCav1 in a mouse model of TDP-43 proteinopathy.

methodsAAV-PhP.eB-SynCav1 was delivered systemically to the TDP-43

resultsSynCav1 exerted robust neuroprotective effects on cognition. Mechanistically, pathological TDP-43 mislocalized to membrane lipid rafts (MLRs), resulting in decreased MLR-associated GluN2A expression and degenerative changes in neuronal ultrastructure. In contrast, SynCav1 delivery alleviated TDP-43 mislocalization on MLRs, stabilized MLR-associated GluN2A expression, and preserved synaptic ultrastructure. Furthermore, SynCav1 mitigated TDP-43-induced mitochondrial hyper-fragmentation and excessive mitochondrial fission signaling. DISCUSSION: These findings establish a novel link between TDP-43 proteinopathy and MLR instability, supporting SynCav1 as a "neuron-centric" candidate for treating TDP-43-related neurodegeneration.

Indexed as

Caveolin 1Cognitive DysfunctionDNA-Binding ProteinsNeurodegenerative DiseasesSynapsinsTDP-43 ProteinopathiesAnimalsBrainDisease Models, AnimalHumansMembrane MicrodomainsMiceMice, TransgenicNeuronsCaveolin 1DNA-Binding ProteinsSynapsinscaveolin‐1gene therapymembrane lipid raftmitochondrial dynamicsneurodegenerationtransactive response DNA‐binding protein 43 proteinopathy

Identifiers

PMID42187024
PMCPMC13238915

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.