Kallikrein-related peptidase 6 in Alzheimer's disease and vascular dementia

Human kallikrein-related peptidase 6 (KLK6) is highly expressed in the central nervous system. Although the physiological roles of this serine protease are unknown, in vitro substrates include amyloid precursor protein and components of the extracellular matrix, which are altered in neurological disease, particularly Alzheimer's disease (AD). We have compared KLK6 expression in post-mortem brain tissue in AD, vascular dementia (VaD) and controls. We studied the distribution of KLK6 in the temporal cortex and white matter by immunohistochemistry, and measured KLK6 mRNA and protein levels in the frontal and temporal cortex from 15 AD, 15 VaD and 15 control brains. Immunohistochemistry showed KLK6 to be restricted to endothelial cells. After adjustment for variations in vessel density by measurement of factor VIII-related antigen, we found KLK6 protein and mRNA levels to be significantly decreased in the frontal but not the temporal cortex in AD. In VaD, KLK6 protein level was significantly increased in the frontal cortex. Our findings suggest that an altered KLK6 expression may contribute to vascular abnormalities in AD and VaD.