Soluble SORL1 in cerebrospinal fluid as a marker for functional impact of rare SORL1 variants - PubMed

8 days ago

Soluble SORL1 (sSORL1) in cerebrospinal fluid (CSF) is studied as a marker for the functional impact of rare SORL1 variants.
The study involved 218 participants, including carriers of SORL1 variants, SORL1-wildtype (WT) Alzheimer's disease (AD) patients, and SORL1-WT controls.
Results showed significantly lower sSORL1 concentrations in carriers of protein-truncating and damaging missense variants.
In SORL1-WT patients, CSF-sSORL1 correlated with pTau181 but not with Aβ42, and levels did not differ between patients and controls.
The findings suggest that impaired SORL1 trafficking reduces receptor delivery to the cell surface, decreasing sSORL1 shedding, supporting its use as a pathway-specific biomarker.
Highlights include ELISA enabling sSORL1 measurement, reduced sSORL1 in pathogenic variant carriers, correlation with tau pathology in AD, and sSORL1 as an in vivo biomarker of SORL1 function.

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