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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 et al.. Alzheimer s & Dementia, 2026-05-01
Topic: Brain proteins, microglia and lab models
SynCav1 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. 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.
Key findings
- SynCav1 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.
- 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.
Why it matters
In this early laboratory work, a treatment called SynCav1 protected thinking and brain cells in models of TDP-43-related damage. These findings are preliminary and support further research into SynCav1 as a possible treatment for TDP-43-related neurodegeneration, but they do not yet show benefit in people.
Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Brian Patrick Head: h-index 44 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42187024) |
| Free to read | 2 / 2 | Free to read |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Wang, D., Ta, V., Wang, H., Ju, J., Wang, C., Chehadeh, C., et al. (2026). Systemic delivery of synapsin‐promoted caveolin‐1 overexpression ameliorates pathological TDP‐43–induced cognitive decline and neurodegenerative changes. Alzheimer s & Dementia. https://doi.org/10.1002/alz.71450
Vancouver
Wang D, Ta V, Wang H, Ju J, Wang C, Chehadeh C, et al. Systemic delivery of synapsin‐promoted caveolin‐1 overexpression ameliorates pathological TDP‐43–induced cognitive decline and neurodegenerative changes. Alzheimer s & Dementia. 2026. doi:10.1002/alz.71450. PMID: 42187024.
BibTeX
@article{wang2026-42187024,
author = {Wang, Dongsheng and Ta, Vinh and Wang, Hongxia and Ju, Jerica and Wang, Chun and Chehadeh, Christine and Torreblanca-Zanca, Albertina and Magaña, Yessenia and others},
title = {{Systemic delivery of synapsin‐promoted caveolin‐1 overexpression ameliorates pathological TDP‐43–induced cognitive decline and neurodegenerative changes}},
journal = {Alzheimer s \& Dementia},
year = {2026},
doi = {10.1002/alz.71450},
pmid = {42187024},
url = {https://doi.org/10.1002/alz.71450}
}
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