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Clinicopathological characterization of vacuolar tauopathy associated with VCP D395G
Ryohei Watanabe, John D. Papatriantafyllou, Kengo Maeda, Geoffrey K. Aguirre, Masahiro Ando, Bernice M. Benoit, Murray Grossman, David John Irwin et al.. Alzheimer s & Dementia, 2025-07-01
Topic: Brain proteins, microglia and lab models
All participants had heterozygous c.1184A > G, p.Asp395Gly in VCP. All symptomatic cases exhibited cognitive, behavioral, and/or language dysfunction indicative of FTD in their 30s to 50s. Neuroimaging studies revealed marked bilateral frontal neurodegeneration and occipital lobar diffusion abnormalities. Post mortem examination of three cases and brain biopsy of one case revealed abundant three- and four-repeat tau deposition and neocortical microvacuolization. Radiological changes were not evident in two pre-symptomatic carriers in their 20s. This study reveals distinct clinical-radiological-pathological correlations in VT, expanding the spectrum of early-onset frontotemporal lobar degeneration (FTLD). HIGHLIGHTS: We characterized the clinical, radiological, and pathological features of vacuolar tauopathy (VT). Five VT cases exhibited a behavioral syndrome, often with aphasic features, with marked frontal lobar atrophy and hypometabolism. Magnetic resonance imaging (MRI) of VT cases revealed occipital lobar diffusion abnormalities. Diffuse neurofibrillary tangles (NFTs) and microvacuolization were observed in the neocortex, with an inverse distribution.
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APA 7th
Watanabe, R., Papatriantafyllou, J. D., Maeda, K., Aguirre, G. K., Ando, M., Benoit, B. M., et al. (2025). Clinicopathological characterization of vacuolar tauopathy associated with VCP D395G. Alzheimer s & Dementia. https://doi.org/10.1002/alz.70427
Vancouver
Watanabe R, Papatriantafyllou JD, Maeda K, Aguirre GK, Ando M, Benoit BM, et al. Clinicopathological characterization of vacuolar tauopathy associated with VCP D395G. Alzheimer s & Dementia. 2025. doi:10.1002/alz.70427. PMID: 40677151.
BibTeX
@article{watanabe2025-40677151,
author = {Watanabe, Ryohei and Papatriantafyllou, John D. and Maeda, Kengo and Aguirre, Geoffrey K. and Ando, Masahiro and Benoit, Bernice M. and Grossman, Murray and Irwin, David John and others},
title = {{Clinicopathological characterization of vacuolar tauopathy associated with VCP D395G}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz.70427},
pmid = {40677151},
url = {https://doi.org/10.1002/alz.70427}
}
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Key findings
- All participants had heterozygous c.1184A > G, p.Asp395Gly in VCP.
- All symptomatic cases exhibited cognitive, behavioral, and/or language dysfunction indicative of FTD in their 30s to 50s.
- Neuroimaging studies revealed marked bilateral frontal neurodegeneration and occipital lobar diffusion abnormalities.
- Post mortem examination of three cases and brain biopsy of one case revealed abundant three- and four-repeat tau deposition and neocortical microvacuolization.
- Radiological changes were not evident in two pre-symptomatic carriers in their 20s.
Why it matters
People with a specific VCP gene change who developed symptoms in their 30s to 50s showed frontotemporal dementia-like dysfunction, frontal neurodegeneration, and tau deposition with microvacuolization. Two presymptomatic carriers in their 20s showed no radiological changes, and the study expands the spectrum of early-onset frontotemporal lobar degeneration.
Study details
- Evidence strengthLow
How this study scored 41/100
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 | 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 | 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 | 2 / 6 | Cited 1.6× 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 | 3 / 4 | Last-listed author Edward B. Lee: h-index 79 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40677151) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
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