We studied amyloid beta protein precursor with Kunitz-type protease inhibitor domains (APPI) concentration in cerebrospinal fluid (CSF) and APPI mRNA in skin fibroblast in Alzheimer's disease (AD). The subjects consisted of AD, cerebrovascular dementia (VD) and age-matched controls. We measured the APPI concentration in the CSF by the trypsin antibody sandwich ELISA. APPI mRNA was examined by the RT-PCR technique. The CSF APPI concentration in AD was significantly higher than that of VD and controls. The CSF APPI concentration in AD was high in the initial stage of dementia and decreased during the course. The expression of APPI mRNA in skin fibroblasts in AD was also significantly higher than that of VD and controls. These results suggest that measurements of APPI levels in CSF and APPI mRNA in skin fibroblasts may be useful for early diagnosis of AD.