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SORL1 variants across Alzheimer's disease European American cohorts.

ABSTRACT: The accumulation of the toxic A? peptide in Alzheimer's disease (AD) largely relies upon an efficient recycling of amyloid precursor protein (APP). Recent genetic association studies have described rare variants in SORL1 with putative pathogenic consequences in the recycling of APP. In this work, we examine the presence of rare coding variants in SORL1 in three different European American cohorts: early-onset, late-onset AD (LOAD) and familial LOAD.

SUBMITTER: Fernandez MV

PROVIDER: S-EPMC5117924 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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SORL1 variants across Alzheimer's disease European American cohorts.

Fernández Maria Victoria MV Black Kathleen K Carrell David D Saef Ben B Budde John J Deming Yuetiva Y Howells Bill B Del-Aguila Jorge L JL Ma Shengmei S Bi Catherine C Norton Joanne J Chasse Rachel R Morris John J Goate Alison A Cruchaga Carlos C

European journal of human genetics : EJHG 20160921 12

The accumulation of the toxic Aβ peptide in Alzheimer's disease (AD) largely relies upon an efficient recycling of amyloid precursor protein (APP). Recent genetic association studies have described rare variants in SORL1 with putative pathogenic consequences in the recycling of APP. In this work, we examine the presence of rare coding variants in SORL1 in three different European American cohorts: early-onset, late-onset AD (LOAD) and familial LOAD. ...[more]

PMID: 27650968

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SORL1 variants and risk of late-onset Alzheimer's disease.

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A comprehensive study of the genetic impact of rare variants in SORL1 in European early-onset Alzheimer's disease.

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SORL1 Polymorphisms in Mexican Patients with Alzheimer's Disease.

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Project description:SORL1 is an element of the amyloid precursor protein processing pathway and is therefore a good candidate for affecting Alzheimer's disease (AD) risk. Indeed, there have been reports of associations between variation in SORL1 and AD risk. We examined six statistically significant single-nucleotide polymorphisms from the initial observation in a large Caucasian American case-controls cohort (1000 late-onset AD [LOAD] cases and 1000 older controls). Analysis of allele, genotype and haplotype frequencies revealed no association with LOAD risk in our cohort.

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Lack of evidence supporting a role for DPP6 sequence variants in Alzheimer's disease in the European American population.

Project description: Not available

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Association between genetic variants in sortilin-related receptor 1 (SORL1) and Alzheimer's disease in adults with Down syndrome.

Project description:Recent reports have suggested that variants in the sortilin-related receptor gene (SORL1) increase the risk of late onset Alzheimer's disease (AD) in Northern European, Hispanic, African-American and Isreali-Arab populations. SORL1 directs trafficking of amyloid precursor protein (APP) and under-expression of SORL1 may lead to over-expression of beta amyloid peptides. Adults with Down syndrome (DS) over-express APP and have early onset and high risk for AD. We investigated the relation of seven variants in the gene for SORL1 to age at onset and risk for AD among 208 adults with DS, 45-70 years of age at baseline. Participants were ascertained through the New York State developmental disability service system and followed at 18-month intervals. Information from cognitive assessments, caregiver interviews, medical record review and neurological examination was used to establish the diagnosis of dementia. Homozygosity for the minor T allele in rs556349 and for the minor C allele in rs536360 was associated with later age at onset and reduced risk of AD (HR=0.26, 95% CI: 0.08-0.86; and HR=0.40, 95% CI: 0.16-0.98, respectively). Mean age at onset was approximately four years later in individuals who were homozygous for those alleles compared with those who had at least one major allele. These findings indicate a modest association of variants in SORL1 with AD. In addition, we did not observe the same alleles to be associated with AD compared with earlier studies, suggesting that these SNPs are in linkage disequilibrium (LD) with the putative functional variants or that expression of the SORL1 gene and hence its interaction with APP might be modified by the extremely high levels of APP characteristic of Down syndrome. Thus, further studies are needed to identify functional variants that influence risk for AD in this uniquely vulnerable population.

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Heterozygous and Homozygous Variants in <i>SORL1</i> Gene in Alzheimer's Disease Patients: Clinical, Neuroimaging and Neuropathological Findings.

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| S-EPMC9024679 | biostudies-literature

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