Home › Research › Inflammation and the immune system
Tau oligomer induced HMGB1 release contributes to cellular senescence and neuropathology linked to Alzheimer's disease and frontotemporal dementia
Gaikwad S, Puangmalai N, Bittar A, Montalbano M, Garcia S, McAllen S, Bhatt N, Sonawane M et al.. Cell reports, 2021-07-01
Topic: Brain proteins, microglia and lab models
Aging, pathological tau oligomers (TauO), and chronic inflammation in the brain play a central role in tauopathies, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). However, the underlying mechanism of TauO-induced aging-related neuroinflammation remains unclear. Here, we show that TauO-associated astrocytes display a senescence-like phenotype in the brains of patients with AD and FTD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Gaikwad, S., Puangmalai, N., Bittar, A., Montalbano, M., Garcia, S., McAllen, S., et al. (2021). Tau oligomer induced HMGB1 release contributes to cellular senescence and neuropathology linked to Alzheimer's disease and frontotemporal dementia. Cell reports. https://doi.org/10.1016/j.celrep.2021.109419
Vancouver
Gaikwad S, Puangmalai N, Bittar A, Montalbano M, Garcia S, McAllen S, et al. Tau oligomer induced HMGB1 release contributes to cellular senescence and neuropathology linked to Alzheimer's disease and frontotemporal dementia. Cell reports. 2021. doi:10.1016/j.celrep.2021.109419. PMID: 34289368.
BibTeX
@article{gaikwad2021-34289368,
author = {Gaikwad, S. and Puangmalai, N. and Bittar, A. and Montalbano, M. and Garcia, S. and McAllen, S. and Bhatt, N. and Sonawane, M. and others},
title = {{Tau oligomer induced HMGB1 release contributes to cellular senescence and neuropathology linked to Alzheimer's disease and frontotemporal dementia}},
journal = {Cell reports},
year = {2021},
doi = {10.1016/j.celrep.2021.109419},
pmid = {34289368},
url = {https://doi.org/10.1016/j.celrep.2021.109419}
}
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.
Key findings
- However, the underlying mechanism of TauO-induced aging-related neuroinflammation remains unclear.
- Here, we show that TauO-associated astrocytes display a senescence-like phenotype in the brains of patients with AD and FTD.
- TauO exposure triggers astrocyte senescence through high mobility group box 1 (HMGB1) release and inflammatory senescence-associated secretory phenotype (SASP), which mediates paracrine senescence in adjacent cells.
- HMGB1 release inhibition using ethyl pyruvate (EP) and glycyrrhizic acid (GA) prevents TauO-induced senescence through inhibition of p38-mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB)-the essential signaling pathways for SASP development.
Why it matters
This study found that tau oligomers trigger astrocytes to release HMGB1, causing a senescence-like state and inflammation in the brains of people with Alzheimer's disease and frontotemporal dementia, and that blocking HMGB1 release reduced this effect. This is early research and does not yet show whether targeting this process would treat or prevent dementia in patients.
Study details
- Evidence strengthLow
How this study scored 49/100
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 (Cell reports) |
| Journal's citation record | 3 / 4 | Cell Reports: journal h-index 321 (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 | 3 / 5 | 2021 — within 6 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 | 5 / 7 | Cited 234 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 33.4 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 16.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 3 / 4 | Cited 157 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Rakez Kayed: h-index 76 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | The University of Texas Medical Branch at Galveston: institution h-index 655 (OpenAlex) |
| Multi-centre 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 34289368) |
| Free to read | 2 / 2 | Free to read |
| Total | 49 / 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).
Related
Studies in the library that share something with this one. The line above each title says what.
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
6 studies in the alzhub library list this one in their references.
Related studies in Inflammation and the immune system
Also tagged “tdp-43”
1,150 studies in the library carry the topic tag “tdp-43”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,150 tagged studies.