Sortilin-related Receptor Research Articles

Impact of SORL1 Single Nucleotide Polymorphisms on Alzheimer’s Disease Cerebrospinal Fluid Markers

Background: Recently, genetic variants of the neuronal sortilin-related receptor with A-type repeats (SORL1, also called LR11 or sorLA) have emerged as risk factors for the development of Alzheimer’s disease (AD). Methods: In this study, SORL1 gene polymorphisms, which have been shown to be related to AD, were analyzed for associations with cerebrospinal fluid (CSF) amyloid beta1–42 (Aβ_1–42), phosphorylated tau181, and total tau levels in a non-Hispanic Caucasian sample, which encompassed 100 cognitively healthy elderly individuals, 166 patients with mild cognitive impairment, and 87 patients with probable AD. The data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu/ADNI). Moreover, the impact of gene-gene interactions between SORL1 single nucleotide polymorphisms (SNPs) and the apolipoprotein E (APOE) Ε4 allele, the major genetic risk factor for sporadic AD, on Aβ_1–42 concentrations was investigated. Results: Significant associations between CSF Aβ_1–42 levels and the SORL1 SNPs 23 (rs3824968) and 24 (rs2282649) were detected in the AD group. The latter association became marginally statistically insignificant after Bonferroni correction for multiple comparisons. Carriers of the SORL1 SNP24 T allele and the SNP23 A allele both had lower CSF Aβ_1–42 concentrations than non-carriers of these alleles. The analysis of the impact of interactions between APOE Ε4 allele and SORL1 SNPs on CSF Aβ_1–42 levels unraveled significant influences of APOE. Conclusions: Our findings provide further support for the notion that SORL1 genetic variants are related to AD pathology, probably by regulating the amyloid cascade.

The role of lipoprotein receptors on the physiological function of APP

In this review, we will primarily focus on the role of members of the low-density lipoprotein receptor (LDL-R) family that are involved in trafficking and processing of the amyloid precursor protein (APP). We will discuss the role of the LDL-receptor family members, low-density lipoprotein receptor-related protein 1 (LRP1), LRP1b, apolipoprotein E receptor 2, sortilin-related receptor (SorLA/LR11) and megalin/LRP2 on the physiological function of APP and its cellular localization. Additionally, we will focus on adaptor proteins that have been shown to influence the physiological function of LDL-R family members in combination with APP processing. The results in this review emphasize that the physiological function of APP cannot be explained by the focus on the APP protein alone but rather in combination with various direct or indirect interaction partners within the cellular environment.

The clinical utility of gene testing for Alzheimer’s disease

Alzheimer's disease (AD) is the largest cause of dementia, affecting 35.6 million people in 2010. Amyloid precursor protein, presenilin 1 and presenilin 2 mutations are known to cause familial early-onset AD, whereas apolipoprotein E (APOE) ε4 is a susceptibility gene for late-onset AD. The genes for phosphatidylinositol-binding clathrin assembly protein, clusterin and complement receptor 1 have recently been described by genome-wide association studies as potential risk factors for late-onset AD. Also, a genome association study using single neucleotide polymorphisms has identified an association of neuronal sortilin related receptor and late-onset AD. Gene testing, and also predictive gene testing, may be of benefit in suspected familial early-onset AD however it adds little to the diagnosis of late-onset AD and does not alter the treatment. We do not recommend APOE ε4 genotyping.

SorLA regulates the activity of lipoprotein lipase by intracellular trafficking

Many different tissues and cell types exhibit regulated secretion of lipoprotein lipase (LPL). However, the sorting of LPL in the trans Golgi network has not, hitherto, been understood in detail. Here, we characterize the role of SorLA (officially known as SorLA-1 or sortilin-related receptor) in the intracellular trafficking of LPL. We found that LPL bound to SorLA under neutral and acidic conditions, and in cells this binding mainly occurred in vesicular structures. SorLA expression changed the subcellular distribution of LPL so it became more concentrated in endosomes. From the endosomes, LPL was further routed to the lysosomes, which resulted in a degradation of newly synthesized LPL. Consequently, an 80% reduction of LPL activity was observed in cells that expressed SorLA. By analogy, SorLA regulated the vesicle-like localization of LPL in primary neuronal cells. Thus, LPL binds to SorLA in the biosynthetic pathway and is subsequently transported to endosomes. As a result of this SorLA mediated-transport, newly synthesized LPL can be routed into specialized vesicles and eventually sent to degradation, and its activity thereby regulated.

SORCS1 alters amyloid precursor protein processing and variants may increase Alzheimer's disease risk.

Sorting mechanisms that cause the amyloid precursor protein (APP) and the β-secretases and γ-secretases to colocalize in the same compartment play an important role in the regulation of Aβ production in Alzheimer's disease (AD). We and others have reported that genetic variants in the Sortilin-related receptor (SORL1) increased the risk of AD, that SORL1 is involved in trafficking of APP, and that underexpression of SORL1 leads to overproduction of Aβ. Here we explored the role of one of its homologs, the sortilin-related VPS10 domain containing receptor 1 (SORCS1), in AD. We analyzed the genetic associations between AD and 16 SORCS1-single nucleotide polymorphisms (SNPs) in 6 independent data sets (2,809 cases and 3,482 controls). In addition, we compared SorCS1 expression levels of affected and unaffected brain regions in AD and control brains in microarray gene expression and real-time polymerase chain reaction (RT-PCR) sets, explored the effects of significant SORCS1-SNPs on SorCS1 brain expression levels, and explored the effect of suppression and overexpression of the common SorCS1 isoforms on APP processing and Aβ generation. Inherited variants in SORCS1 were associated with AD in all datasets (0.001 < p < 0.049). In addition, SorCS1 influenced APP processing. While overexpression of SorCS1 reduced γ-secretase activity and Aβ levels, the suppression of SorCS1 increased γ-secretase processing of APP and the levels of Aβ. These data suggest that inherited or acquired changes in SORCS1 expression or function may play a role in the pathogenesis of AD.

Meta-analysis of the Association Between Variants in SORL1 and Alzheimer Disease

To reexamine the association between the neuronal sortilin-related receptor gene (SORL1) and Alzheimer disease (AD). Comprehensive and unbiased meta-analysis of all published and unpublished data from case-control studies for the SORL1 single-nucleotide polymorphisms (SNPs) that had been repeatedly assessed across studies. Academic research institutions in the United States, the Netherlands, Canada, Belgium, the United Kingdom, Singapore, Japan, Sweden, Germany, France, and Italy. All published white and Asian case-control data sets, which included a total of 12,464 cases and 17,929 controls. Alzheimer disease according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (now known as the Alzheimer's Association). In the white data sets, several markers were associated with AD after correction for multiple testing, including previously reported SNPs 8, 9, and 10 (P < .001). In addition, the C-G-C haplotype at SNPs 8 through 10 was associated with AD risk (P < .001). In the combined Asian data sets, SNPs 19 and 23 through 25 were associated with AD risk (P < .001). The disease-associated alleles at SNPs 8, 9, and 10 (120,873,131-120,886,175 base pairs [bp]; C-G-C alleles), at SNP 19 (120,953,300 bp; G allele), and at SNPs 24 through 25 (120,988,611 bp; T and C alleles) were the same previously reported alleles. The SNPs 4 through 5, 8 through 10, 12, and 19 through 25 belong to distinct linkage disequilibrium blocks. The same alleles at SNPs 8 through 10 (C-G-C), 19 (G), and 24 and 25 (T and C) have also been associated with AD endophenotypes, including white matter hyperintensities and hippocampal atrophy on magnetic resonance imaging, cerebrospinal fluid measures of amyloid β-peptide 42, and full-length SORL1 expression in the human brain. This comprehensive meta-analysis provides confirmatory evidence that multiple SORL1 variants in distinct linkage disequilibrium blocks are associated with AD.

No association of psychosis in Alzheimer disease with neurodegenerative pathway genes

Psychotic symptoms occur in approximately 40% of subjects with Alzheimer disease (AD with psychosis; AD + P) and identify a subgroup with more rapid cognitive decline. We evaluated in 867 AD subjects the association of AD + P with genes which may modify the pathological process via effects on the accumulation of amyloid beta (Aβ) protein and/or hyperphosphorylated microtubule-associated protein tau (MAPT): amyloid precursor protein (APP), beta-site amyloid precursor protein cleaving enzyme (BACE1), sortilin-related receptor (SORL1), and MAPT. Each gene was thoroughly interrogated with tag single-nucleotide polymorphisms (SNPs), and gene-based tests were used to enhance power. We found no association of these genes with AD + P.

The sortilin‐related receptor SORL1 and the amyloid cascade: a possible explanation for the concurrent elevation of CSF soluble APPα and APPβ in Alzheimer's disease

International Journal of Geriatric PsychiatryVolume 25, Issue 5 p. 542-543 Letter to the Editor The sortilin-related receptor SORL1 and the amyloid cascade: a possible explanation for the concurrent elevation of CSF soluble APPα and APPβ in Alzheimer's disease P Alexopoulos, P Alexopoulos Department of Psychiatry and Psychotherapy, Technische Universität München, München, GermanySearch for more papers by this authorA Kurz, A Kurz Department of Psychiatry and Psychotherapy, Technische Universität München, München, GermanySearch for more papers by this authorP Lewczuk, P Lewczuk Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanySearch for more papers by this authorJ Kornhuber, J Kornhuber Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanySearch for more papers by this authorJ Wiltfang, J Wiltfang Department of Psychiatry and Psychotherapy, Universität Duisburg-Essen, Essen, GermanySearch for more papers by this authorW Maier, W Maier Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, GermanySearch for more papers by this authorH Förstl, H Förstl Department of Psychiatry and Psychotherapy, Technische Universität München, München, GermanySearch for more papers by this authorR Perneczky, R Perneczky Department of Psychiatry and Psychotherapy, Technische Universität München, München, Germany Neurobiological Laboratory, Department of Psychiatry and Psychotherapy, Technische Universität München, München, GermanySearch for more papers by this author P Alexopoulos, P Alexopoulos Department of Psychiatry and Psychotherapy, Technische Universität München, München, GermanySearch for more papers by this authorA Kurz, A Kurz Department of Psychiatry and Psychotherapy, Technische Universität München, München, GermanySearch for more papers by this authorP Lewczuk, P Lewczuk Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanySearch for more papers by this authorJ Kornhuber, J Kornhuber Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanySearch for more papers by this authorJ Wiltfang, J Wiltfang Department of Psychiatry and Psychotherapy, Universität Duisburg-Essen, Essen, GermanySearch for more papers by this authorW Maier, W Maier Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, GermanySearch for more papers by this authorH Förstl, H Förstl Department of Psychiatry and Psychotherapy, Technische Universität München, München, GermanySearch for more papers by this authorR Perneczky, R Perneczky Department of Psychiatry and Psychotherapy, Technische Universität München, München, Germany Neurobiological Laboratory, Department of Psychiatry and Psychotherapy, Technische Universität München, München, GermanySearch for more papers by this author First published: 08 April 2010 https://doi.org/10.1002/gps.2349Citations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume25, Issue5May 2010Pages 542-543 RelatedInformation

Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain

BackgroundVariations in sortilin-related receptor (SORL1) expression and function have been implicated in Alzheimers Disease (AD). Here, to gain insights into SORL1, we evaluated SORL1 expression and splicing as a function of AD and AD neuropathology, neural gene expression and a candidate single nucleotide polymorphism (SNP).ResultsTo identify SORL1 splice variants, we scanned each of the 46 internal SORL1 exons in human brain RNA samples and readily found SORL1 isoforms that lack exon 2 or exon 19. Quantification in a case-control series of the more abundant isoform lacking exon 2 (delta-2-SORL1), as well as the "full-length" SORL1 (FL-SORL1) isoform containing exon 2 showed that expression of FL-SORL1 was reduced in AD individuals. Moreover, FL-SORL1 was reduced in cognitively intact individuals with significant AD-like neuropathology. In contrast, the expression of the delta-2-SORL1 isoform was similar in AD and non-AD brains. The expression of FL-SORL1 was significantly associated with synaptophysin expression while delta-2-SORL1 was modestly enriched in white matter. Lastly, FL-SORL1 expression was associated with rs661057, a SORL1 intron one SNP that has been associated with AD risk. A linear regression analysis found that rs661057, synaptophysin expression and AD neuropathology were each associated with FL-SORL1 expression.ConclusionThese results confirm that FL-SORL1 expression declines in AD and with AD-associated neuropathology, suggest that FL-SORL1 declines in cognitively-intact individuals with AD-associated neuropathology, identify a novel SORL1 splice variant that is expressed similarly in AD and non-AD individuals, and provide evidence that an AD-associated SNP is associated with SORL1 expression. Overall, these results contribute to our understanding of SORL1 expression in the human brain.

Implication of Sex and SORL1 Variants in Italian Patients With Alzheimer Disease

To investigate the association of genetic variants in sortilin-related receptor (SORL1), which has been proposed as an important genetic contributor to late-onset Alzheimer disease (LOAD). We analyzed 13 SORL1 single-nucleotide polymorphisms (SNPs) and the relative haplotypes in a case-control association study. The sample included 708 Italian subjects: 251 unrelated, sporadic patients with LOAD, 99 sporadic patients with early-onset Alzheimer disease (AD), and 358 healthy controls. We analyzed the 13 SNPs in the SORL1 gene that had been studied in previous reports using case-control methods and included sex, apolipoprotein E (APOE) genotype, and age at AD onset as covariates. The SNPs 4 (rs661057), 7 (rs12364988), and 10 (rs641120) were significantly associated with LOAD compared with controls. We found an association between these 3 variants and sex, suggesting that SORL1 may possibly affect LOAD through a female-specific mechanism. Of interest, the association of these SNPs with LOAD was confined to APOE epsilon4 noncarriers. Several haplotypic associations at the 5' end of SORL1 were found, including the previously associated CGC haplotype at SNPs 8 through 10. Our results confirm the association of SORL1 with AD and show a possible effect of female sex, suggesting that this gene may be a promising susceptibility factor for LOAD. Further studies to detect pathogenic variants and further elucidate the effect of SORL1 on the development of AD are necessary.

Sequence variation in SORL1 and dementia risk in Swedes

The gene encoding the neuronal sortilin-related receptor SORL1 has been claimed to be associated with Alzheimer's disease (AD) by independent groups and across various human populations. We evaluated six genetic markers in SORL1 in a sample of 1,558 Swedish dementia cases (including 1,270 AD cases) and 2,179 controls. For both single-marker-based and haplotype-based analyses, we found no strong support for SORL1 as a dementia or AD risk-modifying gene in our sample in isolation nor did we observe association with AD/dementia-related traits, including cerebrospinal fluid beta-amyloid(1-42), tau levels, or age at onset. However, meta-analyses of markers in this study together with previously published studies on SORL1 encompassing in excess of 13,000 individuals does suggest significant association with AD (best odds ratio = 1.097; 95% confidence interval = 1.038-1.158, p = 0.001). All six markers were significant in meta-analyses and it is notable that they occur in two distinct linkage disequilibrium blocks. 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.

A Study of the SORL1 Gene in Alzheimer's Disease and Cognitive Function

Several studies have investigated the role of the neuronal sortilin-related receptor (SORL1) gene in Alzheimer's disease (AD), but findings have been inconsistent. 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. We tested for association with AD and cognitive function in 6741 participants of the Rotterdam Study and in 2883 individuals from the Erasmus Rucphen Family study. We performed meta-analyses on AD using our data together with those of previous studies published prior to September 2008 in Caucasians. Further, we studied up to 76 SNPs in a 400 kb region within and flanking the gene to evaluate the evidence that other genetic variants are associated with AD or cognitive function. There was no significant evidence for association between SORL1 SNPs and incident AD patients in the Rotterdam Study. In a meta-analysis of our data with those of others, six out of seven SNPs attained borderline significance. However, removal of the first study reporting association from the meta-analysis resulted in non-significant odds ratios for all SNPs. SNPs rs668387, rs689021, and rs641120 were associated with cognitive function in non-demented individuals at borderline statistical significance in two independent Dutch cohorts, but in the opposite direction. Testing for association using dense SNPs in the SORL1 gene did not reveal significant association with AD, or with cognitive function when adjusting for multiple testing. In conclusion, our data do not support the hypothesis that genetic variants in SORL1 are related to the risk of AD.

The sortilin-related receptor (SORL1) influences variation in memory in late-onset Alzheimer's disease

The sortilin-related receptor (SORL1) influences variation in memory in late-onset Alzheimer's disease

The sortilin-related receptor (SORL1) influences variation in memory in late-onset Alzheimer disease

The sortilin-related receptor (SORL1) influences variation in memory in late-onset Alzheimer disease

SORL1 is genetically associated with Alzheimer disease in a Japanese population

A recent study reported that variants of the neuronal sortilin-related receptor gene ( SORL1) increased the risk of late-onset Alzheimer disease (AD) in several populations. Here, we examined the risk effect in a large, well-characterized group of 437 late-onset AD patients and 451 control subjects in a Japanese population. Among eight single-nucleotide polymorphisms (SNPs) of the SORL1 gene for which association has been reported, we found a significant association for four of them, located between exon 24 and intron 37. This risk was evident in non-carriers of the apolipoprotein E-ɛ4 allele, but not in its carriers. Our results support the evidence that genetic variants of SORL1 affect susceptibility to late-onset AD.

Reduction of SorLA/LR11, a Sorting Protein Limiting β-Amyloid Production, in Alzheimer Disease Cerebrospinal Fluid

The sortilin-related receptor SorLA/LR11 (LR11) is a transmembrane neuronal sorting protein that reduces beta-amyloid precursor protein trafficking to secretases, notably BACE1 that generates beta-amyloid, the principal component of senile plaques in Alzheimer disease (AD). LR11 protein is reduced in patients with late-onset AD, and LR11 polymorphisms have been associated with late-onset AD. T o detect soluble LR11 and APP in cerebrospinal fluid (CSF) from patients with AD and control subjects, as (like beta-amyloid precursor protein) LR11 is cleaved near the membrane to release a large N-terminal fragment that is secreted to media from cultured cells. Case-control study. Academic research. Patients with AD and control subjects. We evaluated CSF LR11, beta-amyloid precursor protein, and apolipoprotein E levels by Western blot in lumbar and postmortem CSF samples. LR11 levels were detectable and stable during 6 months in the CSF of patients with AD. 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). Bivariate analysis with beta-amyloid 42 and LR11 levels improved diagnostic specificity for AD. Reduced LR11 levels are significantly correlated with soluble beta-amyloid precursor protein but not apolipoprotein E levels. Reduced LR11 levels in CSF of patients with AD may have potential as a diagnostic biomarker for patients with LR11 deficits that promote beta-amyloid production or as an index of therapeutic response in late-onset AD.

Genetic Aspects of Alzheimer Disease

Alzheimer disease (AD) is a genetically complex disorder. Mutations in 3 genes, presenilin 1, amyloid precursor protein, and presenilin 2, lead to early-onset familial AD in rare families with onset of disease occurring prior to age 65. Specific polymorphisms in apolipoprotein E are associated with the more common, late-onset AD occurring after age 65. In this review, we discuss current advances in AD genetics, the implications of the known AD genes, presenilin 1, presenilin 2, amyloid precursor protein, and apolipoprotein E, and other possible genes on the clinical diagnosis, treatment, and genetic counseling of patients and families with early- and late-onset AD. In addition to the mutations in 4 known genes associated with AD, mutations in other genes may be implicated in the pathogenesis of the disease. Most recently, 2 different research groups have reported genetic association between 2 genes, sortilin-related receptor and GAB2, and AD. These associations have not changed the diagnostic and medical management of AD. New research in the genetics of AD have implicated novel genes as having a role in the disease, but these findings have not been replicated nor have specific disease causing mutations been identified. To date, clinical genetic testing is limited to familial early-onset disease for symptomatic individuals and asymptomatic relatives and, although not recommended, amyloid precursor protein apolipoprotein E testing as an adjunct to diagnosis of symptomatic individuals.

Association of distinct variants in SORL1 with cerebrovascular and neurodegenerative changes related to Alzheimer disease.

Single-nucleotide polymorphisms (SNPs) in 2 distinct regions of the gene for the sortilin-related receptor (SORL1) (bounded by consecutively numbered SNPs 8-10 and 22-25) were shown to be associated with Alzheimer disease (AD) in multiple ethnically diverse samples. To test the hypothesis that SORL1 is associated with brain magnetic resonance imaging (MRI) measurements of atrophy and/or vascular disease. We evaluated the association of 30 SNPs spanning SORL1 with MRI measures of general cerebral atrophy, hippocampal atrophy, white matter hyperintensities, and overall cerebrovascular disease in 44 African American and 182 white sibships from the MIRAGE Study. We performed single- and 3-SNP haplotype association analyses using family-based tests. Haplotypes found to be significantly associated with at least 1 MRI trait were tested for association with 6 pathological traits in a separate sample of 69 white patients with autopsy-confirmed AD. In white patients, white matter hyperintensities were associated with multiple markers in the region encompassing SNPs 6 to 10, whereas cerebral and hippocampal atrophy were associated with markers from the region including SNPs 21 to 26. Examination of specific 3-SNP haplotypes from these 2 regions in the autopsy-confirmed cases of AD revealed association of white matter disease with SNPs 8 to 10 and association of hippocampal atrophy with SNPs 22 to 26. The haplotype CGC at SNPs 8 to 10 was associated with fewer white matter changes in the clinical (P<.001) and autopsy (P=.02) samples. Variants of SORL1 previously associated with AD are also associated with MRI and neuropathological measures of neurodegenerative and cerebrovascular disease. These findings not only support the hypothesis that multiple areas in SORL1 are of functional importance but also raise the possibility that multiple SORL1 variants influence amyloid precursor protein or endothelial lipoprotein processing or both in different regions of the brain.

The neuronal sortilin-related receptor gene SORL1 and late-onset Alzheimer’s disease

Recent studies indicate that two clusters of single nucleotide polymorphisms in the neuronal sortilin-related receptor gene (SORL1) are causally associated with late-onset Alzheimer's disease (AD). At the cellular level, SORL1 is thought to be involved in intracellular trafficking of amyloid precursor protein. When this gene is suppressed, toxic amyloid beta production is increased, and high levels of amyloid betaare associated with a higher AD risk. Extending the cellular findings, gene expression studies show that SORL1 is differentially expressed in AD patients compared with controls. Furthermore, several genetic studies have identified allelic and haplotypic SORL1 variants associated with late-onset AD, and these variants confer small to modest risk of AD. Taken together, the evidence for SORL1 as a causative gene is compelling. However, putative variants have not yet been identified. Further research is necessary to determine its utility as a diagnostic marker of AD or as a target for new therapeutic approaches.

Genetic Association between SORL1 Polymorphisms and Alzheimer’s Disease in a Japanese Population

Background/Aims: It has recently been shown that the neuronal sortilin-related receptor (SORL1) plays an important role in the pathogenesis of Alzheimer’s disease (AD). Methods: To investigate whether variations around the SORL1 gene are associated with AD, 7 single-nucleotide polymorphisms (SNPs) were genotyped using TaqMan® technology with 180 AD patients and 130 age-matched controls. Results: Our results confirmed the strong linkage disequilibrium among the 7 SNPs studied. However, our study failed to detect any association between the SNPs and AD. We could not confirm any synergetic interaction between the SNPs and apolipoprotein E in our AD patients either. Conclusion: Further genetic studies are needed to clarify the relationship between the SORL1 gene and AD.