Red blood cells are the major source of alpha-synuclein in blood.
BACKGROUND
Alpha-synuclein has been directly linked to Parkinson's disease etiology by mutations in and multiplication of its gene that result in a familial form of Parkinson's disease. Alpha-synuclein has been detected in blood, and was found to be elevated in the blood of those individuals with the alpha-synuclein gene multiplication.


OBJECTIVE
A complete analysis of the level of alpha-synuclein in blood has not been performed. In this report, we determine the quantitative distribution of alpha-synuclein in the plasma and different cellular fractions of human blood. The levels of alpha-synuclein in human and mouse blood are compared.


METHODS
Alpha-synuclein levels in the different fractions of blood were quantified by a sandwich ELISA with purified recombinant alpha-synuclein as an assay standard. Samples were further characterized by Western immunoblot analysis.


RESULTS
More than 99% of the alpha-synuclein resides in the red blood cells (RBCs) with less than 1% of the total detected in the plasma, platelets and peripheral blood mononuclear cells.


CONCLUSIONS
More than 99% of the alpha-synuclein in human blood is present in the peripheral blood cells, with the remainder in plasma. Fractionation of peripheral blood cells from human blood and quantification of alpha-synuclein revealed that only a very small amount of the total alpha-synuclein is present in peripheral blood mononuclear cells, and platelets, with the majority of alpha-synuclein in blood being present in RBCs. Considering the abundance and fragility of RBCs, alpha-synuclein levels in these other blood fractions or other bodily fluids such as cerebrospinal fluid may be artificially elevated by contamination with intact or lysed RBCs.
Barbour
Robin
R
Elan Pharmaceuticals, Inc., South San Francisco, Calif 94080, USA. robin.barbour@elan.com
Kling
Kristin
K
Anderson
John P
JP
Banducci
Kelly
K
Cole
Tracy
T
Diep
Linnea
L
Fox
Michael
M
Goldstein
Jason M
JM
Soriano
Ferdie
F
Seubert
Peter
P
Chilcote
Tamie J
TJ
D000818:Animals; D004912:Erythrocytes / Q000737:chemistry*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D051844:alpha-Synuclein / Q000032:analysis / Q000097:blood*
D051844:alpha-Synuclein