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Advanced Neurology Tau pathology in murine TBI

recent study reported that TDP-43 pathology worsens Availability of data
pTau aggregation and its seeding potential indirectly by
increasing pTau levels. Interestingly, genetic ablation of Not applicable.
110
Sarm1 mitigated both TDP-43 and pTau following closed- References
head TBI, providing the rationale to further investigate
74
the possible interaction between Tau and TDP-43 on 1. Dewan MC, Rattani A, Gupta S, et al. Estimating the
pathology after TBI. global incidence of traumatic brain injury. J Neurosurg.
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4. Conclusion doi: 10.3171/2017.10.JNS17352
It is increasingly understood that human TBI is a major risk 2. Fleminger S, Ponsford J. Long term outcome after traumatic
factor for several neurodegenerative diseases characterized brain injury. BMJ. 2005;331(7530):1419-1420.
by the pathological accumulation of the tau protein. While no doi: 10.1136/bmj.331.7530.1419
single mouse closed-skull TBI model has been shown to fully
replicate all aspects of human TBI-associated tau pathology, 3. Thurman DJ, Alverson C, Dunn KA, Guerrero J, Sniezek JE.
several important parallels exist, as highlighted in this review. Traumatic brain injury in the United States: A public health
These include dysregulation of tau kinases and phosphatases, perspective. J Head Trauma Rehabil. 1999;14(6):602-615.
hyperphosphorylation of tau at different phosphorylation doi: 10.1097/00001199-199912000-00009
sites, the formation of tau oligomers, and the development 4. Faul M, Wald MM, Xu L, Coronado VG. Traumatic Brain
of insoluble aggregates with pathological tau accumulation Injury in the United States: Emergency Department Visits,
in previously unaffected brain areas. While the formation of Hospitalizations, and Deaths, 2002-2006. Atlanta, GA:
paired helical filaments and NFTs has not been conclusively Centers for Disease Control and Prevention; 2010.
demonstrated in wild-type mice, these pathologies have
been replicated in transgenic models. Moreover, the cellular 5. Pugh MJ, Kennedy E, Prager EM, et al. Phenotyping the
spectrum of traumatic brain injury: A review and pathway
and anatomical distribution of tau pathology in mice is to standardization. J Neurotrauma. 2021;38(23):3222-3234.
remarkably similar to the histopathological features used to
define human CTE. Collectively, these findings highlight the doi: 10.1089/neu.2021.0059
translational value of mouse TBI models, enabling researchers 6. LoBue C, Woon FL, Rossetti HC, Hynan LS, Hart J,
to define the mechanisms underlying tau pathology and how Cullum CM. Traumatic brain injury history and progression
these promote neurodegeneration. from mild cognitive impairment to Alzheimer disease.
Neuropsychology. 2018;32(4):401-409.
Acknowledgments
doi: 10.1037/neu0000431
None.
7. Mielke MM, Ransom JE, Mandrekar J, Turcano P, Savica R,
Funding Brown AW. Traumatic brain injury and risk of Alzheimer’s
disease and related dementias in the population. J Alzheimers
None. Dis. 2022;88(3):1049-1059.
Conflict of interest doi: 10.3233/JAD-220159
8. Graham A, Livingston G, Purnell L, Huntley J. Mild
The authors declare that they have no competing interests. Traumatic brain injuries and future risk of developing
Author contributions Alzheimer’s disease: Systematic review and meta-analysis.
J Alzheimers Dis. 2022;87(3):969-979.
Conceptualization: Elif O. Dogan, Aydan Kahriman, Nils doi: 10.3233/JAD-220069
Henninger
Writing – original draft: Elif O. Dogan, Aydan Kahriman 9. Schneider ALC, Selvin E, Latour L, et al. Head injury
Writing – review & editing: Muhammed E. Gunduz, Nils and 25-year risk of dementia. Alzheimers Dement.
Henninger 2021;17(9):1432-1441.
doi: 10.1002/alz.12315
Ethics approval and consent to participate
10. Brett BL, Gardner RC, Godbout J, Dams-O’Connor K,
Not applicable. Keene CD. Traumatic brain injury and risk of
neurodegenerative disorder. Biol Psychiatry. 2022;91(5):
Consent for publication 498-507.
Not applicable. doi: 10.1016/j.biopsych.2021.05.025

Volume 3 Issue 3 (2024) 8 doi: 10.36922/an.3213