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Association between single moderate to severe traumatic brain injury and long-term tauopathy in humans and preclinical animal models: a systematic narrative review of the literature
Walker A, Chapin B, Abisambra J, DeKosky ST.. Acta neuropathologica communications, 2022-01-31
Topic: Brain proteins, microglia and lab models
Background The initiation, anatomic pattern, and extent of tau spread in traumatic brain injury (TBI), and the mechanism by which TBI leads to long-term tau pathology, remain controversial. Some studies suggest that moderate to severe TBI is sufficient to promote tau pathology; however, others suggest that it is simply a consequence of aging. We therefore conducted a systematic narrative review of the literature addressing whether a single moderate to severe head injury leads to long-term development of tauopathy in both humans and animal models. Methods Studies considered for inclusion in this review assessed a single moderate to severe TBI, assessed tau pathology at long-term timepoints post-injury, comprised experimental or observational studies, and were peer-reviewed and published in English. Databases searched included: PUBMED, NCBI-PMC, EMBASE, Web of Science, Academic Search Premiere, and APA Psychnet. Search results were uploaded to Covidence®, duplicates were removed, and articles underwent an abstract and full-text screening process. Data were then extracted and articles assessed for risk of bias. Findings Of 4,150 studies screened, 26 were eligible for inclusion, of which 17 were human studies, 8 were preclinical animal studies, and 1 included both human and preclinical animal studies. Most studies had low to moderate risk of bias. Most human and animal studies (n = 12 and 9, respectively) suggested that a single moderate to severe TBI resulted in greater development of long-term tauopathy compared to no history of head injury. This conclusion should be interpreted with caution, however, due to several limitations: small sample sizes; inconsistencies in controlling for confounding factors that may have affected tau pathology (e.g., family history of dementia or neurological illnesses, apolipoprotein E genotype, etc.), inclusion of mostly males, and variation in reporting injury parameters. Interpretation Results indicate that a single moderate to severe TBI leads to greater chronic development of tauopathy compared to no history of head injury. This implies that tau pathology induced may not be transient, but can progressively develop over time in both humans and animal models. Targeting these tau changes for therapeutic intervention should be further explored to elucidate if disease progression can be reversed or mitigated.
Key findings
- Some studies suggest that moderate to severe TBI is sufficient to promote tau pathology; however, others suggest that it is simply a consequence of aging.
- Search results were uploaded to Covidence®, duplicates were removed, and articles underwent an abstract and full-text screening process.
- Most human and animal studies (n = 12 and 9, respectively) suggested that a single moderate to severe TBI resulted in greater development of long-term tauopathy compared to no history of head injury.
- Interpretation Results indicate that a single moderate to severe TBI leads to greater chronic development of tauopathy compared to no history of head injury.
Why it matters
Of 4,150 studies screened, 26 were reviewed on whether a single moderate to severe head injury leads to long-term tau build-up. Most human and animal studies suggested it does, compared with no head injury, though small samples, mostly male participants and poor control for factors like apolipoprotein E genotype call for caution. The authors suggest tau changes after injury may keep developing over time and could be a target for future treatment research.
Study details
- Study designnarrative review
- Participants12
- Evidence strengthLow
How this study scored 56/100
Published in a peer-reviewed journal, and it is a systematic review of all the studies on the question. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neuropathologica communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A systematic review of all the studies on the question (from PubMed type “Systematic Review”) |
| 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 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 12 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 3 / 7 | Cited 36 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.0 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 2 / 6 | Cited 1.8× 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 | 2 / 4 | Cited 26 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Steven T. DeKosky: h-index 132 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Florida: institution h-index 1,303 (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 35101132) |
| Free to read | 2 / 2 | Free to read |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s40478-022-01311-0
- PubMed: 35101132
- Original source →
- Free full text: Acta Neuropathologica Communications →
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. Check the citation against the original before you use it.
APA 7th
Walker, A., Chapin, B., Abisambra, J., & DeKosky, S. T. (2022). Association between single moderate to severe traumatic brain injury and long-term tauopathy in humans and preclinical animal models: a systematic narrative review of the literature. Acta neuropathologica communications. https://doi.org/10.1186/s40478-022-01311-0
Vancouver
Walker A, Chapin B, Abisambra J, DeKosky ST. Association between single moderate to severe traumatic brain injury and long-term tauopathy in humans and preclinical animal models: a systematic narrative review of the literature. Acta neuropathologica communications. 2022. doi:10.1186/s40478-022-01311-0. PMID: 35101132.
BibTeX
@article{walker2022-35101132,
author = {Walker, A. and Chapin, B. and Abisambra, J. and DeKosky, S. T.},
title = {{Association between single moderate to severe traumatic brain injury and long-term tauopathy in humans and preclinical animal models: a systematic narrative review of the literature}},
journal = {Acta neuropathologica communications},
year = {2022},
doi = {10.1186/s40478-022-01311-0},
pmid = {35101132},
url = {https://doi.org/10.1186/s40478-022-01311-0}
}
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