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The most common type of TBI is mild (mTBI) and often occurs repeatedly among athletes, military personnel, and victims of domestic violence. PD is classically characterized by deficits in fine motor movement control resulting from progressive neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) midbrain region. This neurodegeneration is preceded by the predictable spread of characteristic alpha synuclein (\u03b1Syn) protein inclusions. Whether repetitive mTBI (r-mTBI) can nucleate PD pathology or accelerate prodromal PD pathology remains unknown. To answer this question, an injury device was constructed to deliver a surgery-free r-mTBI to rats and human-like PD pathology was induced by intracranial injection of recombinant \u03b1Syn preformed fibrils. At the 3-month endpoint, the r-mTBI caused encephalomalacia throughout the brain reminiscent of neuroimaging findings in patients with a history of mTBI, accompanied by astrocyte expansion and microglial activation. The pathology associated most closely with PD, which includes dopaminergic neurodegeneration in the SNpc and Lewy body-like \u03b1Syn inclusion burden in the surviving neurons, was not produced de novo by r-mTBI nor was the fibril induced preexisting pathology accelerated. r-mTBI did however cause aggregation of phosphorylated Tau (pTau) protein in nigra of rats with and without preexisting PD-like pathology. pTau aggregation was also found to colocalize with PFF induced \u03b1Syn pathology without r-mTBI. These findings suggest that r-mTBI induced pTau aggregate deposition in dopaminergic neurons may create an environment conducive to \u03b1Syn pathology nucleation and may add to preexisting proteinaceous aggregate burden.<\/jats:p>","DOI":"10.1186\/s40478-022-01475-9","type":"journal-article","created":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T01:19:13Z","timestamp":1669511953000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Repetitive mild TBI causes pTau aggregation in nigra without altering preexisting fibril induced Parkinson\u2019s-like pathology burden"],"prefix":"10.1186","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6248-7318","authenticated-orcid":false,"given":"Vedad","family":"Delic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua H.","family":"Karp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maynard","family":"Guzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel R.","family":"Arismendi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J.","family":"Stalnaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia A.","family":"Burton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen E.","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua P.","family":"Stamos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpine","family":"Sokratian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew B.","family":"West","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Citron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,26]]},"reference":[{"key":"1475_CR1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1176\/jnp.14.2.223","volume":"14","author":"J Parkinson","year":"2002","unstructured":"Parkinson J (2002) An essay on the shaking palsy. 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