Human kallikrein 6 as a biomarker of alzheimer's disease.

OBJECTIVES Alzheimer's disease (AD) is a major cause of dementia in the elderly. It is generally difficult to diagnose accurately early AD. A few biomarkers, including tau protein and amyloid beta-42, are now used as aids for diagnosis and monitoring of AD. Our aim was to examine the possible use of cerebrospinal fluid, blood and tissue, and human kallikrein 6 (hK6) concentration as a marker of AD. METHODS We have used a highly sensitive and specific immunofluorometric procedure for measuring hK6. We measured hK6 in tissue extracts from AD brain or normal individuals, in cerebrospinal fluids of AD patients or normals and in whole blood of AD patients and normals and compared the findings. We have used ten pairs of AD/normal controls in all cases. RESULTS We found that hK6 concentration is tissue extracts from AD brain were approximately twofold lower than extracts from normal controls. Further, we found that cerebrospinal fluid hK6 concentration is approximately a threefold increase, in comparison to cerebrospinal fluid controls (p = 0.001). We have also found that the whole blood hK6 concentration in AD patients is about ten times higher than hK6 concentration in normal controls (p = 0.002). We have immunohistochemically localized the expression of hK6 in epithelial cells of the chorioid plexus. CONCLUSIONS This is the first report describing significant elevations of cerebrospinal fluid and plasma and whole blood hK6 concentration in AD patients, in comparison to controls. These data suggest that hK6 may constitute a new biomarker for diagnosis and monitoring of AD.