We examined whether CSF-sSORL1 can serve as an in vivo marker of genetically impaired SORL1.<h4>Methods</h4>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.<h4>Results</h4>sSORL1 concentrations were significantly lower in carriers of protein-truncating and damaging missense variants. The gene discussed is SORL1; the disease is Alzheimer disease.