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Significance Two of the most important issues in Parkinson’s disease (PD) research are the identification of mechanisms underlying α-synuclein cell-to-cell transfer in the nervous system and the discovery of early diagnostic biomarkers. Both of these issues are addressed in our current manuscript. Using multiple approaches, we present that α-synuclein interacts with lipoproteins within human cerebrospinal fluid and can be taken up by cells in such a state. Moreover, using cerebrospinal fluid samples from 3 large and independent cohorts of patients, we demonstrate that apolipoprotein E is elevated in early, not yet medicated, patients with PD. Finally, using postmortem brain tissue, we provide preliminary histological evidence that apolipoprotein E is enriched in a subpopulation of dopaminergic neurons of human substantia nigra.

α-synuclein−lipoprotein interactions and elevated ApoE level in cerebrospinal fluid from Parkinson's disease patients