Fig 1: sSORL1 concentrations versus pathogenicity category. ELISA measurements of sSORL1 concentrations in CSF derived from carriers of SORL1 genetic variants with different pathogenicity categories or carriers of WT SORL1. Sample size per group: Controls = 50, AD WT = 78, NPV = 14, LPV = 6, MPV = 11, HPV = 18, and PTV = 9. p‐Values were obtained using robust linear models adjusted for age and sex. CSF, cerebrospinal fluid; ELISA, enzyme‐linked immunosorbent assay; HPV, high priority variants; indels, in‐frame insertion deletion variant; LPV, low priority variant; MPV, moderate priority variant; NPV, no priority variant; OR, odds ratio; PTV, protein truncating variant; sSORL1, soluble sortilin‐related receptor; WT, wild‐type. Adjusted significance threshold: 0.000625 < p≤0.00625 = *; 0.0000625 < p≤0.000625 = **; p≤0.0000625 = ***.
Fig 2: The effect of different severity groups versus WT. The effect having a specific SORL1 variant on the CSF‐sSORL1 concentration, as determined by a robust linear regression for CSF‐sSORL1 concentrations between the different severity groups versus WT (SORL1 WT AD cases + controls combined). AD, Alzheimer's disease; CI, confidence interval; CSF, cerebrospinal fluid; SD, standard deviation; SORL1, sortilin‐related receptor; sSORL1, soluble sortilin‐related receptor; WT, wild‐type.
Fig 3: Selection of the study cohort. Participants were included from the Amsterdam Dementia Cohort. SORL1 variant carrier status was determined using whole‐exome sequencing. Samples for which CSF was available were included in the study cohort, WT‐SORL1 included controls, and AD patients (amyloid‐confirmed). A528T, p.Ala528Thr; CSF, cerebrospinal fluid; E270K, p.Glu270Lys; HPV, high priority variants; indels, in‐frame insertion/deletion; LPV, low priority variant; MAF, minor allele frequency; MPV, moderate priority variant; NPV, no priority variant; PTV, protein truncating variant; WT, wild‐type. *Two carriers both carried an E270K and A528T mutation and were included in both groups.
Fig 4: Correlation of sSORL1 levels in SORL1 WT AD patients (n = 78), with age of diagnosis, sex, MMSE, and AD biomarkers. To assess the relationship between CSF‐sSORL1 concentrations and age at diagnosis (A), sex (B). MMSE (C) and AD biomarkers (D)–(F) in SORL1 WT AD, we performed a Robust Linear Model to account for the potential influence of outliers. The association of age of diagnosis with CSF‐sSORL1 was corrected for sex and APOE‐status. The association of sex with CSF‐sSORL1 was corrected for age of diagnosis. The association of MMSE and the AD biomarkers with CSF‐sSORL1 were corrected for age of diagnosis and sex. AD, Alzheimer's disease; CSF, cerebrospinal fluid; MMSE, Mini‐Mental State Examination; SORL1, sortilin‐related receptor sSORL1, soluble sortilin‐related receptor; WT, wild‐type.
Supplier Page from Abcam for Human SORL1 ELISA Kit