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Allelic mRNA expression of sortilin-1 (SORL1) mRNA in Alzheimer's autopsy brain tissues.

ABSTRACT: Polymorphisms in the gene encoding SORL1, involved in cellular trafficking of APP, have been implicated in late-onset Alzheimer's disease, by a mechanism thought to affect mRNA expression. To search for regulatory polymorphisms, we have measured allele-specific mRNA expression of SORL1 in human autopsy tissues from the prefrontal cortex of 26 Alzheimer's patients, and 51 controls, using two synonymous marker SNPs (rs3824968 in exon 34 (11 heterozygous AD subjects and 16 controls), and rs12364988 in exon 6 (8 heterozygous AD subjects)). Significant allelic expression imbalance (AEI), indicative of the presence of cis-acting regulatory factors, was detected in a single control subject, while allelic ratios were near unity for all other subjects. We genotyped 7 SNPs in two haplotype blocks that had previously been implicated in Alzheimer's disease. Since each of these SNPs was heterozygous in several subjects lacking AEI, this study fails to support a regulatory role for SORL1 polymorphisms in mRNA expression.

SUBMITTER: Alachkar H

PROVIDER: S-EPMC2612539 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Allelic mRNA expression of sortilin-1 (SORL1) mRNA in Alzheimer's autopsy brain tissues.

Alachkar Houda H Kataki Maria M Scharre Douglas W DW Papp Audrey A Sadee Wolfgang W

Neuroscience letters 20081015 1

Polymorphisms in the gene encoding SORL1, involved in cellular trafficking of APP, have been implicated in late-onset Alzheimer's disease, by a mechanism thought to affect mRNA expression. To search for regulatory polymorphisms, we have measured allele-specific mRNA expression of SORL1 in human autopsy tissues from the prefrontal cortex of 26 Alzheimer's patients, and 51 controls, using two synonymous marker SNPs (rs3824968 in exon 34 (11 heterozygous AD subjects and 16 controls), and rs12364988 ...[more]

PMID: 18938222

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Project description:BackgroundAlzheimer's disease (AD), the most prevalent form of dementia, affects 6.5 million Americans and over 50 million people globally. Clinical, genetic, and phenotypic studies of dementia provide some insights of the observed progressive neurodegenerative processes, however, the mechanisms underlying AD onset remain enigmatic.AimsThis paper examines late-onset dementia-related cognitive impairment utilizing neuroimaging-genetics biomarker associations.Materials and methodsThe participants, ages 65-85, included 266 healthy controls (HC), 572 volunteers with mild cognitive impairment (MCI), and 188 Alzheimer's disease (AD) patients. Genotype dosage data for AD-associated single nucleotide polymorphisms (SNPs) were extracted from the imputed ADNI genetics archive using sample-major additive coding. Such 29 SNPs were selected, representing a subset of independent SNPs reported to be highly associated with AD in a recent AD meta-GWAS study by Jansen and colleagues.ResultsWe identified the significant correlations between the 29 genomic markers (GMs) and the 200 neuroimaging markers (NIMs). The odds ratios and relative risks for AD and MCI (relative to HC) were predicted using multinomial linear models.DiscussionIn the HC and MCI cohorts, mainly cortical thickness measures were associated with GMs, whereas the AD cohort exhibited different GM-NIM relations. Network patterns within the HC and AD groups were distinct in cortical thickness, volume, and proportion of White to Gray Matter (pct), but not in the MCI cohort. Multinomial linear models of clinical diagnosis showed precisely the specific NIMs and GMs that were most impactful in discriminating between AD and HC, and between MCI and HC.ConclusionThis study suggests that advanced analytics provide mechanisms for exploring the interrelations between morphometric indicators and GMs. The findings may facilitate further clinical investigations of phenotypic associations that support deep systematic understanding of AD pathogenesis.

Dataset Information

Allelic mRNA expression of sortilin-1 (SORL1) mRNA in Alzheimer's autopsy brain tissues.

Publications

Allelic mRNA expression of sortilin-1 (SORL1) mRNA in Alzheimer's autopsy brain tissues.

Similar Datasets

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