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35/100

✓ Peer-reviewed alzhub usefulness score 35 out of 100. Brain tissue and pathology

Topic: Brain proteins, microglia and lab models

Plain-language summary

Chronic cerebral hypoperfusion induced by permanent unilateral common carotid artery occlusion in mice was recently found to induce an age-dependent formation of insoluble cytoplasmic TDP-43 aggregates reminiscent of pathological changes found in human vascular dementia. In this model, the gradual deregulation of TDP-43 homeostasis in cortical neurons was associated with marked cognitive and motor deficits. To target the TDP-43-mediated toxicity in this model, we generated an adeno-associated virus vector encoding a single-chain antibody against TDP-43, called scFv-E6, designed for pan-neuronal transduction following intravenous administration. Injected prior to brain hypoperfusion, this tonic virus-mediated delivery of the scFv-E6 antibody reduced formation of cytoplasmic TDP-43 aggregates in cortical neurons, boosted levels of autophagy markers and attenuated microgliosis. Moreover, the novel object recognition and grip strength tests revealed that neuronal expression of scFv-E6 prevented the cognitive impairment and loss of motor performance caused by two-months of cerebral hypoperfusion. The robust protective effects of scFv-E6 antibody in this model suggest a key role of TDP-43 in neuronal damage and symptom phenotypes caused by chronic cerebral hypoperfusion. Accordingly, TDP-43 should be considered as a new therapeutic target in drug development, including antibody approaches, for treatment of vascular dementia.

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APA 7th

Chami, A. A., Gravel, C., Weng, Y. C., Križ, J., & Julien, J.-P. (2025). Virus-mediated delivery of single-chain antibody targeting TDP-43 protects against neuropathology, cognitive impairment and motor deficit caused by chronic cerebral hypoperfusion. Experimental Neurology. https://doi.org/10.1016/j.expneurol.2025.115138

Vancouver

Chami AA, Gravel C, Weng YC, Križ J, Julien J.-P. Virus-mediated delivery of single-chain antibody targeting TDP-43 protects against neuropathology, cognitive impairment and motor deficit caused by chronic cerebral hypoperfusion. Experimental Neurology. 2025. doi:10.1016/j.expneurol.2025.115138. PMID: 39778789.

BibTeX

@article{chami2025-39778789,
  author  = {Chami, Anna A. and Gravel, Claude and Weng, Yuan Cheng and Križ, Jasna and Julien, Jean-Pierre},
  title   = {{Virus-mediated delivery of single-chain antibody targeting TDP-43 protects against neuropathology, cognitive impairment and motor deficit caused by chronic cerebral hypoperfusion}},
  journal = {Experimental Neurology},
  year    = {2025},
  doi     = {10.1016/j.expneurol.2025.115138},
  pmid    = {39778789},
  url     = {https://doi.org/10.1016/j.expneurol.2025.115138}
}

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What the evidence grade means here

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Key findings

In this model, the gradual deregulation of TDP-43 homeostasis in cortical neurons was associated with marked cognitive and motor deficits.
Moreover, the novel object recognition and grip strength tests revealed that neuronal expression of scFv-E6 prevented the cognitive impairment and loss of motor performance caused by two-months of cerebral hypoperfusion.

Why it matters

In a mouse model of chronic cerebral hypoperfusion, virus-mediated delivery of a single-chain antibody against TDP-43 reduced cytoplasmic TDP-43 aggregates and prevented cognitive impairment and motor deficits. These results suggest TDP-43 should be considered a therapeutic target, but the work is in mice and not yet tested in humans.

Study details

Evidence strengthLow

How this study scored 35/100

Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Experimental Neurology)
Journal's citation record	3 / 4	Experimental Neurology: journal h-index 271 (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	4 / 5	2025 — within 3 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)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	1 / 7	Cited 3 times (OpenAlex, 2026-10-10)
Citations per year	1 / 5	1.0 citations a year over 3 year(s) since 2025
Impact for its field and year	1 / 6	Cited 0.9× 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	1 / 4	Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	1 / 4	Last-listed author Jean-Pierre Julien: h-index 15 (OpenAlex, whole career)
Institution's track record	1 / 3	Université Laval: institution h-index 823 (OpenAlex)
Multicenter collaboration	0 / 3	OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete)
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 39778789)
Free to read	2 / 2	Free to read
Total	35 / 100	—

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