![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
6MB |
![[thumbnail of Supporting Information]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supporting Information)
8MB |
| Item Type: | Article |
|---|---|
| Title: | Familial Alzheimer disease mutation identifies novel role of SORLA in release of neurotrophic exosomes |
| Creators Name: | Juul-Madsen, Kristian, Rudolph, Ina-Maria, Gomes, Jemila P., Meyer, Katrina, Ovesen, Peter L., Gorniak-Walas, Malgorzata, Kokoli, Marianna, Telugu, Narasimha S., vonTangen Sivertsen, Malthe, Febbraro, Fabia, Sutherland, Duncan S., Palmfeldt, Johan, Diecke, Sebastian, Andersen, Olav M., Selbach, Matthias and Willnow, Thomas E. |
| Abstract: | INTRODUCTION: Mutations in SORL1, encoding the sorting receptor Sortilin-related receptor with A-type repeats (SORLA), are found in individuals with Alzheimer's disease (AD). We studied SORLA(N1358S), carrying a mutation in its ligand binding domain, to learn more about receptor functions relevant for human brain health. METHODS: We investigated consequences of SORLA(N1358S) expression in induced pluripotent stem cell (iPSC)-derived human neurons and microglia, using unbiased proteome screens and functional cell assays. RESULTS: We identified alterations in the SORLA(N1358S) interactome linked to biogenesis of exosomes. Consequently, the mutant receptor failed to promote release and neurotrophic qualities of exosomes, a defect attributed to altered exosomal content of microRNAs controlling neuronal maturation. DISCUSSION: We identified a role for SORLA in controlling quantity and neurotrophic quality of exosomes secreted by cells, suggesting impaired cellular cross talk through exosomes as a pathological trait contributing to AD pathology in carriers of SORL1 variants. |
| Keywords: | Alzheimer’s Disease, Exosomes, IPSC Models, Microglia, Multi-Omics |
| Source: | Alzheimer's & Dementia |
| ISSN: | 1552-5260 |
| Publisher: | Wiley |
| Volume: | 21 |
| Number: | 9 |
| Page Range: | e70591 |
| Date: | 10 September 2025 |
| Official Publication: | https://doi.org/10.1002/alz.70591 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
