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

Abstract

BackgroundThe 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.MethodsEight 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.ResultsAmong 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.ConclusionsFindings 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.

Levels of plasma neurofilament light chain and cognitive function in patients with Alzheimer or Parkinson disease

“…Analysis of the results collected for MCI and AD patients did not indicate that APOE ɛ4 carriers had higher plasma NFL than non-carriers. These findings are different from previous studies which suggested MCI patients had higher plasma NFL levels than HC and APOE ɛ4 carriers had higher plasma NFL than non-carriers 1 , which may reflect the highly nuanced and complex clinical entity in MCI 23 and relatively low proportion of APOE ɛ4 carriers among the Asian AD and MCI groups 24 – 27 .…”

Genetics of neuropsychiatric symptoms in patients with Alzheimer's disease: A 1‐year follow‐up study

“…Our previous study also reported an association between SORL1 and AD, although at the rs1784933 and rs2298813 loci. 6 Those results emphasized the roles of SORL1 also for NPS of AD. Compared with studies in other ethnic populations, the reference allele for the SORL1 rs3824968 was the A, not T, in all subpopulations of the Chinese population.…”

“…The studies we have conducted have demonstrated that the sortilin-related receptor 1 gene (SORL1) and the ATP-binding cassette, subfamily A, member 7 gene (ABCA7) are associated with AD. 5,6 Whether these high-risk genes are also involved in the presentation of NPS is not clear. For instance, the results for the apolipoprotein E (APOE) gene were inconsistent [7][8][9][10] and the evidence summarized recently in a meta-analysis revealed a negative finding.…”

Association between SORL1 polymorphisms and the risk of Alzheimer’s disease

“…Additionally, Kimura et al [18], Feng et al [19], Shibata et al [20] and Wen et al [23] agreed that there is no association between rs689021 and AD. However Cousin et al [11], Ryan et al [24], Lee et al [25], Reynolds et al [26], Rowland et al [27], Lee et al [28], Cellini et al [29], and Chou et al [30] found a significant association between rs689021 and AD. It was the current authors who first analyzed the association between rs689021 and AD and reported that SNP rs689021 was associated with a decreased risk to AD among Caucasians.…”

“…It is widely accepted that SORL1 plays a significant role in AD pathogenesis [30]. The meta-analysis reported here included data from different ethnicities, thus may provide a fresh perspective into the association between SORL1 gene and AD risk.…”