Abnormal serum concentrations of proteins in Parkinson's disease.
Blood serum was used to identify protein biomarkers for diagnosis of Parkinson's disease (PD) using analytically validated quantitative 2D-gel electrophoresis, and single variable and multivariate statistics. Using banked samples from a first medical center, we identified 57 specific protein spot biomarkers with disease-specific abnormal levels in serum of patients with PD, Alzheimer's disease, amyotrophic lateral sclerosis and similar neurodegenerative conditions (337 samples), when compared to age-matched normal controls (132 samples). To further assess their clinical usefulness in Parkinson's disease, we obtained prospective newly drawn blood serum samples from a second (56 PD, 30 controls) and third (6 PD, 48 controls) medical center. The protein concentrations of the 57 biomarkers were assessed by 2D-gel electrophoresis. Stepwise linear discriminant analysis selected a combination of 21 of the 57 as optimal to distinguish PD patients from controls. When applied to the samples from the second site, the 21 proteins had sensitivity of 93.3% (52 of 56 PD correctly classified), specificity of 92.9% (28 of 30 controls correctly classified); 15 of 15 patients with mild, 28 of 30 with moderate to severe symptoms, and all of the 6 PD patients from the third site were correctly classified. Eleven of the 21 proteins showed statistically significant abnormal concentrations in patients with mild symptoms, and 14 in patients with moderate-severe symptoms. The protein identities reflect the heterogeneity of Parkinson's disease, and thus may provide the capability of monitoring the blood for a diverse range of PD pathophysiological mechanisms: cellular degeneration, oxidative stress, inflammation, and transport.
Goldknopf
Ira L
IL
Power3 Medical Products, Inc., The Woodlands, TX 77381, USA. igoldknopf@power3medical.com
Bryson
Jennifer K
JK
Strelets
Irina
I
Quintero
Silvia
S
Sheta
Essam A
EA
Mosqueda
Miguel
M
Park
Helen R
HR
Appel
Stanley H
SH
Shill
Holly
H
Sabbagh
Marwan
M
Chase
Bruce
B
Kaldjian
Eric
E
Markopoulou
Katerina
K
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood*
D015415:Biomarkers; D001798:Blood Proteins