P3-086: CSF levels of PSA and PSA-ACT complexes in Alzheimer's disease

Background: Alpha1-antichymotrypsin (ACT) is found in amyloid plaques of Alzheimer’s disease (AD), but not in other types of amyloid. AD patients have higher cerebrospinal fluid (CSF) levels of ACT than controls. The exact role of ACT in AD is not clear, ACT functions as a serine protease inhibitor and is able to form complexes with, and to inactivate serine proteases. Prostate specific antigen (PSA) is a serine protease mainly found complexed to ACT in serum. PSA is found in the human brain and CSF, therefore the aim of this study was to determine if PSA is also the target protease of ACT in AD brain and if PSA-ACT complex levels in CSF can be used as biomarker for AD. Methods: Levels of ACT and PSA-ACT in CSF and serum samples of AD patients (n 16), mild cognitive impaired (MCI) subjects (n 19) and controls (n 12) were determined by sandwich ELISA. Total PSA was detemined in a competitive immunoassay and albumin with nephelometry in an array protein system. Statistical analysis was performed using SPSS software 15.0 and Medcalc. Results: ACT-PSA complexes and total PSA, were detectable in CSF of most male, but of only very few women. PSA levels in CSF and serum highly correlated (r 0.88; p 0.001) and Passing and Bablock regression analysis showed no deviation from zero regarding the intercept. Moreover, no indications for the presence of PSA in brain tissue were found by immunohistochemical analysis. CSF levels of either ACT, PSA or PSA-ACT did not differ between AD, MCI and control groups. Conclusions: PSA in CSF is not locally produced in the brain, but derived from the blood. Furthermore, PSA-ACT complexes are not suitable as a biomarker in AD.