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To unravel the underlying molecular pathways, we conducted a proteomic analysis of the putamen and the entorhinal cortex, two brain regions carrying notable \u03b1-syn pathology. We demonstrate that distinct assemblies of \u03b1-syn aggregates drive unique pathogenic changes that ultimately result in a comparable extent of nigrostriatal degeneration at the level of nigral dopaminergic neuron cell bodies and striatal dopaminergic terminals. More broadly, our findings identify pathogenic trajectories associated with large or small \u03b1-syn aggregates, suggesting the existence of several possible concomitant pathogenic routes in PD.<\/jats:p>","DOI":"10.1126\/sciadv.adu6050","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T14:00:58Z","timestamp":1750255258000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["Differential pathological dynamics triggered by distinct Parkinson patient\u2013derived \u03b1-synuclein extracts in nonhuman primates"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7737-6837","authenticated-orcid":true,"given":"R.","family":"Kinet","sequence":"first","affiliation":[{"name":"Univ. 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