Electrophoretic separation of amyloid beta peptides in plasma.
In this prospective study, for the first time we have separated and quantified amyloid beta (Abeta) peptides in the plasma of patients with Alzheimer's disease (AD, n = 8) and age- and environment-matched healthy controls (n = 9) with urea-based Abeta-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)/immunoblot. In addition to the Abeta peptides 1-37/38/39/40/42, which we recently identified as regular constituents of human cerebrospinal fluid (CSF), we have observed a novel electrophoretic band migrating slightly cathodically to Abeta1-42. Since a standard peptide with the amino acid sequence Abeta2-40 migrates in the same position, we hypothesize that this plasma-specific band may correspond to Abeta2-40. The concentration of Abeta peptides in the plasma has been approximately 100-fold lower compared to the CSF. Interestingly, the concentration of the two shortest peptides and the longest one of these considered here (i.e., Abeta1-37/38/42) have increased significantly when the samples have been frozen at -80 degrees C before immunoprecipitation, while the 'middle-length' peptides (i.e., Abeta1-39/40) have not been affected by this procedure. We have not observed significant differences of the Abeta peptides concentrations between AD and control subjects. Our method can be used to investigate the significance of plasma Abeta peptides in neurodegenerative disorders, and to monitor the efficiency of drugs with beta/gamma-secretase inhibitory potency.
Lewczuk
Piotr
P
Department of Psychiatry and Psychotherapy, Molecular Neurobiology Lab, University of Erlangen-Nuernberg, Erlangen, Germany.
Esselmann
Hermann
H
Bibl
Mirko
M
Paul
Sabine
S
Svitek
Jana
J
Miertschischk
Johannes
J
Meyrer
Robert
R
Smirnov
Alexandr
A
Maler
Juan Manuel
JM
Klein
Christian
C
Otto
Markus
M
Bleich
Stefan
S
Sperling
Wolfgang
W
Kornhuber
Johannes
J
Rüther
Eckhard
E
Wiltfang
Jens
J
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000276:immunology / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood* / Q000276:immunology / Q000302:isolation & purification
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments