SORL1 is genetically associated with Alzheimer disease in a Japanese population

Kimura, Ryo; Yamamoto, Mitsuko L.; Morita, Takashi; Akatsu, Hiroyasu; Kudo, Takashi; Kamino, Kouzin; Takeda, Masatoshi

doi:10.1016/j.neulet.2009.06.014

Cited by 49 publications

(38 citation statements)

References 26 publications

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“…It is located on chromosome 11q23.2-q24.2 and encodes a membrane protein which is specifically expressed in neurons. Several studies have replicated the initial observation of the genetic association between SORL1 and AD [3][4][5][6][7][8][9][10][11][12][13] . Nonetheless, no general consensus on the role of SORL1 genetic variants as risk factors for AD exists, since other investigations only found weak or no associations between SORL1 genetic variants and AD [14][15][16][17][18][19] .…”

Section: Introductionmentioning

confidence: 77%

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

Alexopoulos

Guo²,

Kratzer³

et al. 2011

Dement Geriatr Cogn Disord

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ciations between CSF A ␤ 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 A ␤ 1-42 concentrations than noncarriers of these alleles. The analysis of the impact of interactions between APOE 4 allele and SORL1 SNPs on CSF A ␤ 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.Copyright © 2011 S. Karger AG, Basel Key WordsDementia ؒ Mild cognitive impairment ؒ Healthy aging ؒ Amyloid cascade ؒ Association Abstract 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 (A ␤ 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) 4 allele, the major genetic risk factor for sporadic AD, on A ␤ 1-42 concentrations was investigated. Results: Significant asso-

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Section: Introductionmentioning

confidence: 77%

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

Alexopoulos

Guo²,

Kratzer³

et al. 2011

Dement Geriatr Cogn Disord

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“…Genotyping of KIBRA rs17070145 polymorphism was performed by the Taq-Man SNP assay and ABI Prism 7900HT sequence detection system (Applied Biosystems, Foster City, Calif., USA) as previously described [20][21][22][23] . The apolipoprotein E (APOE) genotype was determined by the PCR-RFLP method [20][21][22][23] .…”

Section: Genotypingmentioning

confidence: 99%

<i>KIBRA</i> Genetic Polymorphism Influences Episodic Memory in Alzheimer’s Disease, but Does Not Show Association with Disease in a Japanese Cohort

Hayashi¹,

Kazui²,

Kamino³

et al. 2010

Dement Geriatr Cogn Disord

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Background/Aims: A single-nucleotide polymorphism (SNP) in the KIBRA gene, rs17070145, was reported to be significantly associated with episodic memory in cognitively normal cohorts. This observation has expanded genetic studies on KIBRA to Alzheimer’s disease (AD). Importantly, the association between KIBRA and episodic memory in AD has never been addressed. In this study, we investigated whether the KIBRA rs17070145 SNP influences AD episodic memory and the disease in a Japanese cohort. Methods: Blood samples from 346 AD patients and 375 normal cognitive controls were collected and genotyped for rs17070145. Episodic memory was measured in 32 AD patients, diagnosed for the first time, by use of the Rivermead Behavioral Memory Test (RBMT). Results: We found that KIBRA C allele carriers scored significantly lower than KIBRA non-C carriers on both RBMT total profile score (p = 0.042, effect size = 0.84) and RBMT total screening score (p < 0.001, effect size = 1.42). The KIBRA gene did not show association with AD in our Japanese cohort. Conclusion: Our results evidence a strong association between the KIBRA gene and episodic memory impairment in AD, but show no influence on AD in our Japanese cohort. We propose that KIBRA might have an effect similar to cognitive reserve.

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“…But when restricted to AD and MCI, SORL1 was associated with MCI but not with AD. SORL1 has been reported to affect AD in different population but replication studies have given inconsistent results [3][4][5][6][7]14]. The meta-analysis study by Reitz and colleagues suggested that negative findings were likely related to underpowered studies with small sample sizes, allelic heterogeneity, or both.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the APOE isoform may have a modifying effect on the association of SORL1 and APOE; specifically, effects of distinct SORL1 SNPs may be weakened by the APOE-4 allele. Several studies showed association of SORL1 SNPs with AD in APOE-4 noncarriers [7,21].…”

Section: Discussionmentioning

confidence: 99%

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Polymorphisms in the Sortilin-Related Receptor 1 Gene Are Associated with Cognitive Impairment in Filipinos

Casingal

Daroy

Mapua

et al. 2014

Asian Journal of Neuroscience

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Background/Aims. Sortilin-related receptor 1 (SORL1) is involved in the neuronal transport processes and plays a role in the formation of amyloid plaques. This study investigated the association of 6 SORL1 single nucleotide polymorphisms (SNPs 8,9,10,13,19, and 23) with cognitive impairment (CI) in Filipinos. Methods. DNA samples from 484 subjects (100 Alzheimer's Disease (AD) cases, 109 mild cognitive impairment (MCI) cases, 18 other types of CI, and 257 no dementia controls (NDC)) were genotyped using TaqMan SNP Genotyping Assays. Data Analysis. Our study showed strong linkage disequilibrium in the SNPs 8, 9, and 10 block. Our results showed that CI was significantly associated with SNPs 13 and 23. None of the SORL1 SNPs studied was associated with AD while SNPs 8, 9, 10, and 23 were associated with MCI. Conclusion. The findings had provided evidence that SORL1 may predispose individuals to CI. Further studies are needed to clarify the role of SORL1 in Filipinos with AD.

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SORL1 is genetically associated with Alzheimer disease in a Japanese population

Cited by 49 publications

References 26 publications

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

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

<i>KIBRA</i> Genetic Polymorphism Influences Episodic Memory in Alzheimer’s Disease, but Does Not Show Association with Disease in a Japanese Cohort

Polymorphisms in the Sortilin-Related Receptor 1 Gene Are Associated with Cognitive Impairment in Filipinos

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