Here, we show that LR11 deficiency in this AD mouse model significantly increases Abeta levels and exacerbates early amyloid pathology in brain, causing a forward shift in disease onset that is LR11 gene dose-dependent.
Hereby we review the evidence of the association of SORL1 common and rare variants with AD risk and conduct a meta-analysis of published data on SORL1 rare variants in five large sequencing studies.
Furthermore, we found that SORL1 promoter DNA methylation might act as one of the mechanisms responsible for the differences in expression observed between blood and brain for both healthy elderly and AD patients groups.
We conducted a study of 7 single nucleotide polymorphisms (SNPs), rs668387, rs689021, rs641120, rs1699102, rs3824968, rs2282649, and rs1010159, in the SORL1 gene that were associated to AD in previous studies.
Furthermore, peptides related to amyloid-β protein precursor (AβPP) processing [e.g., soluble AβPPα and β (sAβPPα and sAβPPβ, respectively); sortilin-related receptor with A-type repeats (SORL1, also called LR11 or SORLA)] are factors crucially implicated in the formation of pathological hallmarks of AD.
Recently, polymorphisms across the neuronal sortilin-related receptor (SORL1) gene were shown to be significantly associated with AD in several cohorts.
Taken together, these findings confirm that SORL1 is associated with AD and might be a potential tool for identifying MCI subjects at high risk of conversion to AD.
These data are consistent with either allelic heterogeneity or the existence of as yet untested functional variants and these will be important considerations in further attempts to evaluate the importance of sequence variation in SORL1 with AD risk.
This comprehensive meta-analysis provides confirmatory evidence that multiple SORL1 variants in distinct linkage disequilibrium blocks are associated with AD.
Sex-specific characterization and evaluation of the Alzheimer's disease genetic risk factor sorl1 in zebrafish during aging and in the adult brain following a 100 ppb embryonic lead exposure.
Comprehensive screening for point mutations was carried out by direct sequencing of coding regions in the three known AD causative genes: PSEN1, PSEN2, APP, as well as the AD associated gene SORL1.