Amyloid beta1-40 quantification in CSF: comparison between chromatographic and immunochemical methods.
OBJECTIVE
Amyloid beta (Abeta) is the principal component of senile plaques, one of the hallmarks of Alzheimer's disease (AD). Evidence is accumulating that soluble aggregates (oligomers) of Abeta are important in the pathogenesis of AD.


METHODS
We compared three different methods for quantification of the 40 amino acid form of Abeta (Abeta40) in CSF, two based on antibodies [ELISA and surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF) with antibody-coated arrays] and one based on direct binding of proteins to a protein array [SELDI-TOF and immobilized metal affinity [copper] (IMAC30)].


RESULTS
CSF Abeta40 concentration was only found to be significantly elevated in AD (127% of control levels; p=0.0095) using SELDI-TOF with IMAC30 arrays.


CONCLUSIONS
These data suggest that the measured Abeta level in CSF may differ depending on whether antibody-based methods are used or not, possibly caused by epitope masking due to Abeta oligomerization or to binding of Abeta to carrier proteins.
Simonsen
A H
AH
Biomarker Discovery Center Facility, Ciphergen, Copenhagen, Denmark. asimonsen@ciphergen.com
Hansson
S F
SF
Ruetschi
U
U
McGuire
J
J
Podust
V N
VN
Davies
H A
HA
Mehta
P
P
Waldemar
G
G
Zetterberg
H
H
Andreasen
N
N
Wallin
A
A
Blennow
K
K
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D002555:Cerebrospinal Fluid / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007120:Immunochemistry / Q000379:methods; D008297:Male; D010446:Peptide Fragments / Q000032:analysis* / Q000134:cerebrospinal fluid; D012016:Reference Values; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)