Deposition of amyloid beta-protein in senile plaque cores and cerebral vessels is a major neuropathological finding of Alzheimer's disease (AD). Three species of cDNA clones encoding amyloid beta-protein precursors (APP 695, APP 751 and APP 770) were isolated and sequenced. We examined quantitatively the expression of these APP mRNAs in autopsied brains (frontal cortex) of AD patients and control subjects, using Northern blot analysis and the ribonuclease protection assay. Northern blot analysis revealed the production of three types of APP mRNA in the human brain and that AD/control ratios were 2.04 for APP 770 mRNA, 1.11 for APP 751 mRNA and 1.12 for APP 695 mRNA. In the protection assay the ratio of APP 770/APP 751/APP 695 mRNA was approximately 1:10:20 in the brain of control and the AD/control ratios were 2.38, 1.30 and 0.81 for APP 770, APP 751 and APP 695 mRNAs, respectively. These results suggested that an increase in APP 770 and APP 751, harboring a protease inhibitor domain, may disturb the balance between biosynthesis and degradation of APPs, which might lead to amyloid deposition.