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A central role of \u03b1\u2010synuclein in the selective neurodegeneration of Parkinson's disease has been speculated, as its level of expression critically determines the propensity of this protein to misfold. To investigate whether the propensity of neuronal cell loss is associated with the level of endogenous \u03b1\u2010synuclein expression, non\u2010transgenic rats were given a single intravenous administration of \u03b1\u2010synuclein pre\u2010formed fibrils (PFFs) reversibly complexed with the rabies virus glycoprotein peptide (RVG9R). The number of surviving cells in different neuronal populations was systematically quantified using unbiased stereology. Our data demonstrated that a non\u2010selective, transvascular delivery of \u03b1\u2010synuclein PFFs led to a time\u2010dependent loss of specific populations of midbrain (but not olfactory) dopaminergic neurons, medullary (but not pontine) cholinergic neurons, and brainstem serotonergic neurons. Contrary to the central role of endogenous \u03b1\u2010synuclein expression in determining the seeding and aggregation propensity of pathological \u03b1\u2010synuclein, we did not observe an association between the levels of \u03b1\u2010synuclein expression in different regions of the rodent brain (although did not ascertain this at the individual cell level) and neurodegenerative propensity. The results from our study highlight the complexity of the neurodegenerative process generated by \u03b1\u2010synuclein seeding. Further investigations are therefore required to elucidate the molecular basis of neurodegeneration driven by exogenous pathogenic \u03b1\u2010synuclein spread.<\/jats:p>","DOI":"10.1111\/bpa.13128","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T03:10:59Z","timestamp":1667358659000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Selective neurodegeneration generated by intravenous \u03b1\u2010synuclein pre\u2010formed fibril administration is not associated with endogenous \u03b1\u2010synuclein levels in the rat brain"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0273-1320","authenticated-orcid":false,"given":"Wei\u2010Li","family":"Kuan","sequence":"first","affiliation":[{"name":"John van Geest Centre for Brain Repair, Department of Clinical Neuroscience University of Cambridge  Cambridge 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Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaline V.","family":"Fazal","sequence":"additional","affiliation":[{"name":"John van Geest Centre for Brain Repair, Department of Clinical Neuroscience University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline H.","family":"Williams\u2010Gray","sequence":"additional","affiliation":[{"name":"John van Geest Centre for Brain Repair, Department of Clinical Neuroscience University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger A.","family":"Barker","sequence":"additional","affiliation":[{"name":"John van Geest Centre for Brain Repair, Department of Clinical Neuroscience University of Cambridge  Cambridge UK"},{"name":"Department of Neurology Addenbrooke's Hospital  Cambridge UK"},{"name":"Wellcome Trust MRC Cambridge Stem Cell Centre  Cambridge 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