Distribution of Alzheimer's disease amyloid A4-generating enzymes in rat brain tissue

To screen for putative amyloid A4-splitting proteinases, model peptide substrates homologous to the N- and C-terminal portions of the A4 protein were synthesized. The N-terminal A4-splitting enzyme activity was found to be higher in the hypothalamus and limbic area, compared with in the cerebral cortex and cerebellum in 2-month-old rat. The activity decreased throughout the brain in 20-month-old rat. On the other hand, the activity of the putative C-terminal A4-splitting enzyme was significantly higher, 1.4-fold, in the hippocampus than in the cerebral cortex in the young rat. The activity also significantly decreased in the brain of 20-month-old rat, but was still higher in the cerebral cortex, hippocampus and cerebellum.