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The pathological aggregation of this protein is a hallmark of synucleinopathies such as Parkinson's disease (PD) or Multiple System Atrophy (MSA). Misfolded aSyn, which primarily originates in the cell cytosol, transmits between neurons, promoting a prion\u2010like propagation. However, extracellular environments such as interstitial and cerebrospinal fluids (ISF &amp; CSF) play a major role in its clearance and pathological transformation. The molecular components of CSF, including proteins, glycosaminoglycans, and metal ions, may influence the aggregate morphology, structure, and cytotoxicity to cells. To better understand how extracellular composition affects aggregates and their formation, artificial cerebrospinal fluid (aCSF) is employed to mimic potential aggregation processes occurring in CSF. Distinct aSyn fibrils are observed that exhibited low stability outside aCSF, and the removal of key CSF components led to its structural alterations. Cryo\u2010electron microscopy revealed that these fibrils possess an electron density pocket coordinated with polar basic AAs (K43, K45, H50) that is also observed in aggregates obtained from PD and MSA patients. 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