CSF levels of PSA and PSA–ACT complexes in Alzheimer’s disease

This version was published on 1 November 2009

Ann Clin Biochem 2009;46:477-483
doi:10.1258/acb.2009.009130
© 2009 Association for Clinical Biochemistry

 

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Original Articles


Sandra D Mulder1,4,
Johannes A Heijst1,4,
Cees Mulder1,4,
Frans Martens1,
C Erik Hack1,
Philip Scheltens2,4,
Marinus A Blankenstein1,4 and
Robert Veerhuis1,3,4


1 Department of Clinical Chemistry;
2 Department of Neurology;
3 Department of Psychiatry;
4 Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands


Corresponding author: Sandra D Mulder, Department of Clinical Chemistry, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Email: sd.mulder{at}vumc.nl


Background: Prostate-specific antigen (PSA) is a serine protease that inserum, is predominantly found complexed to the serine proteaseinhibitor alpha1-antichymotrypsin (ACT). ACT co-localizes withamyloid plaques in Alzheimer’s disease (AD) brain and both PSAand ACT are detectable in cerebrospinal fluid (CSF). Therefore,we aimed to determine whether PSA is produced in the brain andwhether PSA and PSA–ACT complex levels in CSF can be usedas 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 temporalcortex 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 almostall male and only very few female subjects. The levels of PSAand PSA–ACT complexes in CSF did not differ between AD,FTLD, MCI and control groups. PSA CSF/serum quotients highlycorrelated with albumin CSF/serum quotients. Furthermore, thehydrodynamic radius of PSA was found to be 3 nm and the theoreticalPSA quotient, derived from the Felgenhauer plot, correspondedwell with the measured PSA quotient.

Conclusions: PSA is locally produced in the human brain; however, brain PSAhardly contributes to the CSF levels of PSA. PSA and PSA–ACTlevels in CSF are not suitable as a biomarker for AD.


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