Somatostatin slows Aβ plaque deposition in aged APP NL-F/NL-F mice by blocking Aβ aggregation
Abstract The neuroendocrine peptide somatostatin (SST) has long been thought of as influencing the deposition of the amyloid β peptide (Aβ) in Alzheimer’s disease (AD). Missing have been in vivo data in a relevant Aβ amyloidosis model. Here we crossed App NL-F/NL-F mice with Sst-deficient mice to as...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-29559-z |
| _version_ | 1811165958652297216 |
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| author | Declan Williams Bei Qi Yan Hansen Wang Logine Negm Christopher Sackmann Claire Verkuyl Vanessa Rezai-Stevens Shehab Eid Nimit Vediya Christine Sato Joel C. Watts Holger Wille Gerold Schmitt-Ulms |
| author_facet | Declan Williams Bei Qi Yan Hansen Wang Logine Negm Christopher Sackmann Claire Verkuyl Vanessa Rezai-Stevens Shehab Eid Nimit Vediya Christine Sato Joel C. Watts Holger Wille Gerold Schmitt-Ulms |
| author_sort | Declan Williams |
| collection | DOAJ |
| description | Abstract The neuroendocrine peptide somatostatin (SST) has long been thought of as influencing the deposition of the amyloid β peptide (Aβ) in Alzheimer’s disease (AD). Missing have been in vivo data in a relevant Aβ 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 Aβ 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 Aβ amyloid plaques. Follow-on western blot analyses of whole brain extracts indicated that Sst interferes with early steps of Aβ 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 Aβ amyloid plaque formation through direct interference with Aβ aggregation rather than through its effects on neprilysin expression. |
| first_indexed | 2024-04-10T15:44:36Z |
| format | Article |
| id | doaj.art-c75b27984a3d486f870a342af747fc07 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-10T15:44:36Z |
| publishDate | 2023-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c75b27984a3d486f870a342af747fc072023-02-12T12:12:24ZengNature PortfolioScientific Reports2045-23222023-02-0113111610.1038/s41598-023-29559-zSomatostatin slows Aβ plaque deposition in aged APP NL-F/NL-F mice by blocking Aβ aggregationDeclan Williams0Bei Qi Yan1Hansen Wang2Logine Negm3Christopher Sackmann4Claire Verkuyl5Vanessa Rezai-Stevens6Shehab Eid7Nimit Vediya8Christine Sato9Joel C. Watts10Holger Wille11Gerold Schmitt-Ulms12Tanz Centre for Research in Neurodegenerative Diseases, University of TorontoTanz Centre for Research in Neurodegenerative Diseases, University of TorontoTanz Centre for Research in Neurodegenerative Diseases, University of TorontoTanz Centre for Research in Neurodegenerative Diseases, University of TorontoTanz Centre for Research in Neurodegenerative Diseases, University of TorontoTanz Centre for Research in Neurodegenerative Diseases, University of TorontoTanz Centre for Research in Neurodegenerative Diseases, University of TorontoTanz Centre for Research in Neurodegenerative Diseases, University of TorontoTanz Centre for Research in Neurodegenerative Diseases, University of TorontoTanz Centre for Research in Neurodegenerative Diseases, University of TorontoTanz Centre for Research in Neurodegenerative Diseases, University of TorontoCentre for Prions and Protein Folding Diseases, University of AlbertaTanz Centre for Research in Neurodegenerative Diseases, University of TorontoAbstract The neuroendocrine peptide somatostatin (SST) has long been thought of as influencing the deposition of the amyloid β peptide (Aβ) in Alzheimer’s disease (AD). Missing have been in vivo data in a relevant Aβ 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 Aβ 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 Aβ amyloid plaques. Follow-on western blot analyses of whole brain extracts indicated that Sst interferes with early steps of Aβ 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 Aβ amyloid plaque formation through direct interference with Aβ aggregation rather than through its effects on neprilysin expression.https://doi.org/10.1038/s41598-023-29559-z |
| spellingShingle | Declan Williams Bei Qi Yan Hansen Wang Logine Negm Christopher Sackmann Claire Verkuyl Vanessa Rezai-Stevens Shehab Eid Nimit Vediya Christine Sato Joel C. Watts Holger Wille Gerold Schmitt-Ulms Somatostatin slows Aβ plaque deposition in aged APP NL-F/NL-F mice by blocking Aβ aggregation Scientific Reports |
| title | Somatostatin slows Aβ plaque deposition in aged APP NL-F/NL-F mice by blocking Aβ aggregation |
| title_full | Somatostatin slows Aβ plaque deposition in aged APP NL-F/NL-F mice by blocking Aβ aggregation |
| title_fullStr | Somatostatin slows Aβ plaque deposition in aged APP NL-F/NL-F mice by blocking Aβ aggregation |
| title_full_unstemmed | Somatostatin slows Aβ plaque deposition in aged APP NL-F/NL-F mice by blocking Aβ aggregation |
| title_short | Somatostatin slows Aβ plaque deposition in aged APP NL-F/NL-F mice by blocking Aβ aggregation |
| title_sort | somatostatin slows aβ plaque deposition in aged app nl f nl f mice by blocking aβ aggregation |
| url | https://doi.org/10.1038/s41598-023-29559-z |
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