α-Synuclein Interacts with Lipoproteins in Plasma

Area of Science:

• Neuroscience
• Biochemistry
• Molecular Biology

Background:

• Parkinson's disease (PD) involves brain cell death and alpha-synuclein (α-syn) aggregation.
• Alpha-synuclein (α-syn) is a potential blood biomarker for PD.
• The mechanism of α-syn crossing the blood-brain barrier (BBB) is unknown.

Purpose of the Study:

• To investigate the mechanism by which α-syn may cross the BBB.
• To test the hypothesis that α-syn interacts with lipoproteins for BBB transport.

Main Methods:

• Co-immunocapture assays of α-syn with plasma proteins.
• Western blotting of plasma fractions separated by gel filtration.

Main Results:

• Alpha-synuclein (α-syn) co-immunocaptured with apoE, apoJ, and apoA1, but not apoB, in human plasma.
• Western blotting confirmed α-syn association with high-density lipoproteins (HDL).
• Alpha-synuclein (α-syn) and ApoJ were detected in lipoprotein (a) (Lp(a)) fractions.

Conclusions:

• Results strongly support the hypothesis that α-syn interacts with HDL.
• This interaction may facilitate α-syn transport across the BBB.
• Findings have implications for understanding PD pathogenesis and biomarker development.