assess

For translation and biomarker development, the best program is biochemical fractionation of patient CSF coupled to structural and seeding assays. The field does not need another bulk-correlative proteomics pass first; it needs causal fraction-addback experiments that identify which fractions preserve the fibril polymorph and which do not.

Lipoprotein and EV models rank highest because they provide concrete, purifiable material and a direct route to structural validation by cryo-EM, proteomics, and serial seeding. If a stabilizing cofactor can be isolated, it becomes both a mechanistic clue to in vivo templating and a potential biomarker axis for synucleinopathy subtype stratification.