(2015) dissect the function of common non-coding risk haplotypes in the SORL1 locus in the pathogenesis of sporadic Alzheimer's disease using patient-derived induced pluripotent stem cells.
LR11 levels were significantly reduced in lumbar samples from patients with mild to moderate probable AD, as well as in ventricular CSF from patients with autopsy-confirmed AD (predominantly Braak stage III-IV).
LR11 (SorLA) is a recently identified neuronal protein that interacts with amyloid precursor protein (APP), a central player in the pathology of the Alzheimer's disease (AD).
SorLA has recently attracted much attention as a novel strong risk gene for Alzheimer's disease, and much effort is currently being put into understanding the underlying molecular mechanism.
According to our findings, SORL1 variations influence the atrophy of specific AD-related brain structures, which suggested the potential role of SORL1 in the neurodegeneration of cognitive related regions.
Although our analysis of pooled samples has positive results for the association between SORL1 and AD, there is substantial heterogeneity across studies.
Altogether, five loci (rs6656401 at CR1, rs983392within MS4A6A, rs11218343 at SORL1, rs6733839 at BIN1, and APOE ε4) have been detected to be associated with one or a few established AD-related neuroimaging measures.
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.