| First Author | Williams D | Year | 2023 |
| Journal | Sci Rep | Volume | 13 |
| Issue | 1 | Pages | 2337 |
| PubMed ID | 36759538 | Mgi Jnum | J:336272 |
| Mgi Id | MGI:7433806 | Doi | 10.1038/s41598-023-29559-z |
| Citation | Williams D, et al. (2023) Somatostatin slows Abeta plaque deposition in aged APP(NL-F/NL-F) mice by blocking Abeta aggregation. Sci Rep 13(1):2337 |
| abstractText | The neuroendocrine peptide somatostatin (SST) has long been thought of as influencing the deposition of the amyloid beta peptide (Abeta) in Alzheimer's disease (AD). Missing have been in vivo data in a relevant Abeta amyloidosis model. Here we crossed App(NL-F/NL-F) mice with Sst-deficient mice to assess if and how the presence of Sst influences pathological hallmarks of Abeta amyloidosis. We found that Sst had no influence on whole brain neprilysin transcript, protein or activity levels, an observation that cannot be accounted for by a compensatory upregulation of the Sst paralog, cortistatin (Cort), that we observed in 15-month-old Sst-deficient mice. Sst-deficiency led to a subtle but significant increase in the density of cortical Abeta amyloid plaques. Follow-on western blot analyses of whole brain extracts indicated that Sst interferes with early steps of Abeta assembly that manifest in the appearance of SDS-stable smears of 55-150 kDa in Sst null brain samples. As expected, no effect of Sst on tau steady-state levels or its phosphorylation were observed. Results from this study are easier reconciled with an emerging body of data that point toward Sst affecting Abeta amyloid plaque formation through direct interference with Abeta aggregation rather than through its effects on neprilysin expression. |
