CSF levels of PSA and PSA-ACT complexes in Alzheimer's disease.
BACKGROUND
Prostate-specific antigen (PSA) is a serine protease that in serum, is predominantly found complexed to the serine protease inhibitor alpha1-antichymotrypsin (ACT). ACT co-localizes with amyloid plaques in Alzheimer's disease (AD) brain and both PSA and ACT are detectable in cerebrospinal fluid (CSF). Therefore, we aimed to determine whether PSA is produced in the brain and whether PSA and PSA-ACT complex levels in CSF can be used as a biomarker for AD.


METHODS
Levels of ACT and PSA-ACT were determined by sandwich enzyme-linked immunosorbent assay in CSF and serum samples of AD (n = 16), frontotemporal lobe dementia (FTLD) (n = 19), mild cognitively impaired (MCI) patients (n = 19) and controls (n = 12). Total PSA was determined in a non-competitive immunoassay. Reverse transcriptase-polymerase chain reaction (RT-PCR) for PSA was performed on postmortem hippocampus and temporal cortex specimens from control and AD cases.


RESULTS
PSA is expressed in the brain, as detected by RT-PCR. PSA and PSA-ACT complexes were detectable in CSF of almost all male and only very few female subjects. The levels of PSA and PSA-ACT complexes in CSF did not differ between AD, FTLD, MCI and control groups. PSA CSF/serum quotients highly correlated with albumin CSF/serum quotients. Furthermore, the hydrodynamic radius of PSA was found to be 3 nm and the theoretical PSA quotient, derived from the Felgenhauer plot, corresponded well with the measured PSA quotient.


CONCLUSIONS
PSA is locally produced in the human brain; however, brain PSA hardly contributes to the CSF levels of PSA. PSA and PSA-ACT levels in CSF are not suitable as a biomarker for AD.
Mulder
Sandra D
SD
Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands. sd.mulder@vumc.nl
Heijst
Johannes A
JA
Mulder
Cees
C
Martens
Frans
F
Hack
C Erik
CE
Scheltens
Philip
P
Blankenstein
Marinus A
MA
Veerhuis
Robert
R
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D003072:Cognition Disorders / Q000134:cerebrospinal fluid; D003704:Dementia / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D017430:Prostate-Specific Antigen / Q000134:cerebrospinal fluid*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013050:Spectrometry, Fluorescence / Q000379:methods; D013702:Temporal Lobe / Q000473:pathology; D000514:alpha 1-Antichymotrypsin / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D000514:alpha 1-Antichymotrypsin; D017430:Prostate-Specific Antigen