Sorl1 as an Alzheimer's disease predisposition gene?
ABSTRACT Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressively disabling impairments in memory, cognition, and non-cognitive behavioural symptoms. Sporadic AD is multifactorial and genetically complex. While several monogenic mutations cause early-onset AD and gene alleles have been suggested as AD susceptibility factors, the only extensively validated susceptibility gene for late-onset AD is the apolipoprotein E (APOE) epsilon4 allele. Alleles of the APOE gene do not account for all of the genetic load calculated to be responsible for AD predisposition. Recently, polymorphisms across the neuronal sortilin-related receptor (SORL1) gene were shown to be significantly associated with AD in several cohorts. Here we present the results of our large case-control whole-genome scan at over 500,000 polymorphisms which presents weak evidence for association and potentially narrows the association interval.
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ABSTRACT: Abstract The neuronal sortilin-related receptor (SORL1) has been reported to modulate the risk of Alzheimer's disease (AD) in a variety of populations, but replication studies have been inconsistent. Amnestic mild cognitive impairment (aMCI) is characterized by episodic memory impairment and represents the prodromal stage of AD. However, the relationship between SORL1 and aMCI remains unclear. This study aimed to investigate the relationship between SORL1 genetic variation and aMCI in the Han Chinese population. We conducted a case-control study using a single-nucleotide polymorphism (SNP), rs668387 (SNP8), in the 5' region of SORL1, and three SNPs (rs2070045 (SNP19), rs3824968 (SNP23), rs2282649 (SNP24)) in the 3' region of SORL1, along with a haplotype analysis, in 139 aMCI patients and 213 cognitively-healthy controls from a northern Han Chinese population. We observed that SNP19 had a significantly different allele frequency between aMCI patients and controls (P = 0.006). Moreover, the GAT haplotype at SNPs 19-23-24 was associated with an increased risk of aMCI (odds ratio 1.377), while the TTC haplotype at SNPs 19-23-24 was associated with a decreased risk (odds ratio 0.708). These results indicated that the SNPs in the 3' region of SORL1 are associated with aMCI in northern Han Chinese.The International journal of neuroscience 10/2013; · 0.86 Impact Factor
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ABSTRACT: Late-onset Alzheimer's Disease (LOAD) is a common neurodegenerative disease, and the two well identified pathological hallmarks of LOAD are senile plaques formed from amyloid β peptides (Aβ) and neurofibrillary tangles (NFTs) consisting of hyperphorylated tau protein. The neuronal Sortilin-related Receptor (SORL1) is involved in the processing and trafficking of amyloid precursor protein (APP) into recycling pathways, thus influencing Aβ generation and by this AD pathology. To explore the relationship between the single nucleotide polymorphism (SNP) of the SORL1 SNP 19 rs2070045 and LOAD, a case-control study was conducted in a Chinese Han cohort including 77 LOAD patients and 100 control participants. This SNP 19 rs2070045 was genotyped with a polymerase chain reaction-restriction fragment length polymorphism, (PCR-RFLP) method. The association was revealed between the polymorphism of SNP 19 rs2070045 (T/T, T/G, G/G) and the risk of LOAD. The results of this study indicated that the T allele (T/G+T/T) of SNP 19 rs2070045 was successful in exerting obvious influence in LOAD patients (χ2=4.884, P=0.027<0.05). However, there is no sufficient evidence to prove that the T allele of SNP 19 rs2070045 is associated with ɛ4 allele of ApoE gene in LOAD patients (χ2=0.771, P=0.380>0.05).Neuroscience Letters 12/2013; · 2.03 Impact Factor
- Internal Medicine News 11/2007; 40(21):45-45.