Soluble SORL1 in cerebrospinal fluid as a marker for functional impact of rare SORL1 variants
| Authors | |
|---|---|
| Year of publication | 2026 |
| Type | Article in Periodical |
| Magazine / Source | ALZHEIMERS & DEMENTIA |
| MU Faculty or unit | |
| Citation | |
| web | https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.71042 |
| Doi | https://doi.org/10.1002/alz.71042 |
| Keywords | Alzheimer's Disease; cerebrospinal fluid (CSF); missense variants; quantitative immunoassay; soluble SORL1 (sSORL1); SORL1 |
| Description | INTRODUCTION: The sortilin-related receptor (SORL1) directs APP and A beta trafficking within the retromer pathway. Cleavage at the cell surface releases soluble SORL1 (sSORL1) into cerebrospinal fluid (CSF). We examined whether CSF-sSORL1 can serve as an in vivo marker of genetically impaired SORL1. METHODS: CSF-sSORL1 was quantified by enzyme-linked immunosorbent assay (ELISA) in 218 participants: 90 carriers of SORL1 variants, 78 SORL1-wildtype (WT) AD patients, and 50 SORL1-WT controls. RESULTS: sSORL1 concentrations were significantly lower in carriers of protein-truncating and damaging missense variants. In SORL1-WT patients, CSF-sSORL1 correlated with pTau181 but not with A beta 42 among AD patients, and did not differ between patients and controls. DISCUSSION: These findings suggest that impaired SORL1 trafficking reduces receptor delivery to the cell surface and thereby decreases sSORL1 shedding, supporting its potential use as a pathway-specific biomarker. |
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