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Cerebrovascular p16INK4A expression induces cerebral small vessel disease-related phenotypes
Keiji Kawatani, Tomonori Aikawa, Zeynab Tabrizi, Yining Pan, Yingxue Ren, Ni Wang, Aishe Kurti, Toshihiko Nambara et al.. Acta neuropathologica communications, 2025-08-12
Topic: Inflammation, microglia and astrocytes
Cerebral small vessel disease (cSVD) is the most common cause of vascular cognitive impairment and dementia (VCID) and highly associated with Alzheimer's disease pathogenesis. There is an urgent need to establish relevant animal models for cSVD. As aging is the strongest risk factor for these diseases, cerebrovascular senescence is implicated in cSVD pathogenesis. We investigated how AAV-based expression of senescence marker CDKN2A/p16INK4A in cerebrovascular endothelial cells influences cSVD phenotypes in adult wild-type mice. A single intraperitoneal injection of the AAV carrying CDKN2A/p16INK4A caused blood-brain barrier impairments, neurovascular uncoupling, and reduction of cerebral blood flow, accompanied with behavioral changes in mice. While single cell RNA-sequencing and immunostaining revealed the upregulation of VCAM1 in cerebrovascular endothelial cells, in vivo two-photon excitation microscopy detected aggravated leukocyte adhesions to capillaries. Our findings demonstrate the contributions of p16INK4A in cerebrovascular endothelial cells to cSVD and VCID pathogenesis through new mouse model.
Key findings
- Cerebral small vessel disease (cSVD) is the most common cause of vascular cognitive impairment and dementia (VCID) and highly associated with Alzheimer's disease pathogenesis.
- While single cell RNA-sequencing and immunostaining revealed the upregulation of VCAM1 in cerebrovascular endothelial cells, in vivo two-photon excitation microscopy detected aggravated leukocyte adhesions to capillaries.
- Our findings demonstrate the contributions of p16INK4A in cerebrovascular endothelial cells to cSVD and VCID pathogenesis through new mouse model.
Study details
- Evidence strengthLow
How this study scored 43/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neuropathologica communications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40796891) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Kawatani, K., Aikawa, T., Tabrizi, Z., Pan, Y., Ren, Y., Wang, N., et al. (2025). Cerebrovascular p16INK4A expression induces cerebral small vessel disease-related phenotypes. Acta neuropathologica communications. https://doi.org/10.1186/s40478-025-02085-x
Vancouver
Kawatani K, Aikawa T, Tabrizi Z, Pan Y, Ren Y, Wang N, et al. Cerebrovascular p16INK4A expression induces cerebral small vessel disease-related phenotypes. Acta neuropathologica communications. 2025. doi:10.1186/s40478-025-02085-x. PMID: 40796891.
BibTeX
@article{kawatani2025-40796891,
author = {Kawatani, Keiji and Aikawa, Tomonori and Tabrizi, Zeynab and Pan, Yining and Ren, Yingxue and Wang, Ni and Kurti, Aishe and Nambara, Toshihiko and others},
title = {{Cerebrovascular p16INK4A expression induces cerebral small vessel disease-related phenotypes}},
journal = {Acta neuropathologica communications},
year = {2025},
doi = {10.1186/s40478-025-02085-x},
pmid = {40796891},
url = {https://doi.org/10.1186/s40478-025-02085-x}
}
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