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Background  The sortilin-related receptor 1 ( SORL1 ) gene, regulating the trafficking and recycling of amyloid precursor protein, has been related to Alzheimer’s disease (AD) and mild cognitive impairment (MCI). The aim of the present study was to investigate the relationship between  SORL1  polymorphisms, plasma concentrations of amyloid-beta (Aβ) isoforms, and AD and MCI susceptibility for a Han Chinese population in Taiwan.    Methods  Eight single-nucleotide polymorphisms (SNPs) in  SORL1  and the apolipoprotein E gene ( APOE ) ε4 alleles were genotyped in 798 patients with AD, 157 patients with MCI, and 401 control subjects. Plasma concentrations of Aβ42, Aβ40, and neuropsychiatric tests for six different cognitive domains were examined.    Results  Among the eight tested SNPs,  SORL1  rs1784933 was most significantly associated with AD and MCI in our population. The G allele of rs1784933 exerted a protective effect and was associated with a reduced risk of AD (odds ratio [OR] = 0.75,  p  = 0.004) and MCI (OR = 0.69,  p  = 0.013). The significance remained after we adjusted for age, sex, and  APOE  ε4 alleles. For the overall participants, the plasma concentrations of Aβ42 were nominally significant for subjects carrying the rs1784933 G allele having a lower level than those without the G allele ( p  = 0.046). There was a similar trend for the G allele carriers to have a lower plasma Aβ40 level than noncarriers, but this was not significant. The nonsynonymous SNP rs2298813 was also related to a lower disease risk when AD and MCI were combined as a group (OR = 0.76,  p  = 0.035). However, there was no association between  SORL1  genotypes and any of the six cognitive tests.    Conclusions  Findings from our study provide support for the effect of  SORL1  gene on the disease risks and pathognomonic surrogates of AD/MCI. The interaction between  SORL1  polymorphisms and Aβ formation requires further study.

SORL1 gene, plasma biomarkers, and the risk of Alzheimer’s disease for the Han Chinese population in Taiwan