Expression of neprilysin, somatostatin and the somatostatin sst5 receptor in the hippocampal formation of brains from Alzheimer's disease patients

摘要

Background: In Alzheimer's disease (AD), the accumulation of amyloid beta (Abeta) in the brain is thought to be the primary pathogenic agent in the AD cascade. The following have been proposed as potential therapeutic strategies in AD: (i) protease inhibitors, including beta secretase and gamma secretase; (ii) Abeta vaccination; and (iii) inhibitors of Ap agglutination. However, as yet there are no studies demonstrating successful suppression of A beta accumulation in AD brains. Neprilysin (NEP), a neutral endopeptidase, is a major Ap-degrading enzyme that is activated by somatostatin (SST). It is thought that NEP may be a therapeutic agent against AD, but the role of SST in AD brains has not been sufficiently elucidated to date. Thus, in the present study, we compared the expression of SST, the sst receptor, and NEP in the hippocampal formation in brains from both AD patients and normal controls using immunohistochemical techniques.Methods: Twelve human brains (six control brains and six AD brains) were used in the present study. The diagnosis of AD was made according to the Braak stage. Control brains were selected from cases with no cognitive impairment clinically that were classified as being at Braak neurofibrillary tangle (NFT) Stage II. The AD brains were selected from cases classified as greater than Braak NFT Stage IV.Results: In the present study, SST and sst receptor-like immunoreactivity was significantly reduced in AD brains compared with normal brains. Although NEP-like immunoreactivity was also significantly reduced in AD brains compared with normal brains, in the CA4 region NEP was preserved in the hippocampal formation of AD brains.Conclusion: These results suggest that the origin of the A accumulated may be correlated with the reduction of the SST neuronal network in AD brains. Activating intrinsic NEP through the SST neuronal system may contribute to a reduction in the risk of AD. Further investigations into the role SST receptors may provide n...