Home › Research › Brain tissue and pathology
Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology
Rissman RA, Poon WW, Blurton-Jones M, Oddo S, Torp R, Vitek MP, LaFerla FM, Rohn TT et al.. The Journal of clinical investigation, 2004-07-01
Topic: Brain proteins, microglia and lab models
Neurofibrillary tangles (NFTs) are composed of abnormal aggregates of the cytoskeletal protein tau. Together with amyloid beta (Abeta) plaques and neuronal and synaptic loss, NFTs constitute the primary pathological hallmarks of Alzheimer disease (AD). Recent evidence also suggests that caspases are activated early in the progression of AD and may play a role in neuronal loss and NFT pathology.
Key findings
- Together with amyloid beta (Abeta) plaques and neuronal and synaptic loss, NFTs constitute the primary pathological hallmarks of Alzheimer disease (AD).
- Recent evidence also suggests that caspases are activated early in the progression of AD and may play a role in neuronal loss and NFT pathology.
- Here we demonstrate that tau is cleaved at D421 (DeltaTau) by executioner caspases.
- Following caspase-cleavage, DeltaTau facilitates nucleation-dependent filament formation and readily adopts a conformational change recognized by the early pathological tau marker MC1.
Why it matters
This study demonstrates that tau is cleaved at D421 by executioner caspases, and that following caspase-cleavage, the truncated tau facilitates filament formation. This suggests caspase-cleavage of tau is an early event in Alzheimer's disease tangle pathology.
Study details
- Evidence strengthLow
How this study scored 50/100
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 (The Journal of clinical investigation) |
| Journal's citation record | 4 / 4 | Journal of Clinical Investigation: journal h-index 706 (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 | 1 / 5 | 2004 — older than 20 years, still counted |
| 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 | 6 / 7 | Cited 460 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.2 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 4 / 6 | Cited 12.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 2 / 4 | Cited 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Carl W. Cotman: h-index 166 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Duke Medical Center: institution h-index 1,255 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15232619) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 50 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1172/jci20640
- PubMed: 15232619
- Original source →
- Free full text: Journal of Clinical Investigation →
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
Rissman, R. A., Poon, W. W., Blurton-Jones, M., Oddo, S., Torp, R., Vitek, M. P., et al. (2004). Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology. The Journal of clinical investigation. https://doi.org/10.1172/jci20640
Vancouver
Rissman RA, Poon WW, Blurton-Jones M, Oddo S, Torp R, Vitek MP, et al. Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology. The Journal of clinical investigation. 2004. doi:10.1172/jci20640. PMID: 15232619.
BibTeX
@article{rissman2004-15232619,
author = {Rissman, R. A. and Poon, W. W. and Blurton-Jones, M. and Oddo, S. and Torp, R. and Vitek, M. P. and LaFerla, F. M. and Rohn, T. T. and others},
title = {{Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology}},
journal = {The Journal of clinical investigation},
year = {2004},
doi = {10.1172/jci20640},
pmid = {15232619},
url = {https://doi.org/10.1172/jci20640}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
10 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Brain tissue and pathology
Also tagged “phosphorylated”
732 studies in the library carry the topic tag “phosphorylated”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 732 tagged studies.