Biomarker for successful aging without cognitive decline

Abstract

Methods and compositions for determining whether a subject will age without developing cognitive decline are provided. An exemplary method includes detecting one or more allelic variants in a gene encoding low density lipoprotein-related protein 1B. In a preferred embodiment, the detecting step is accomplished by contacting a sample obtained from the subject with a probe that forms a detectable complex with a nucleic acid in the sample containing an allelic variant indicative of aging without developing cognitive decline, wherein detection of the allelic variant in the sample indicates that the subject will age without developing cognitive decline.

1 . A method for identifying a human subject with an increased chance of reaching 85 without developing cognitive decline comprising:
 assaying a biological sample obtained from the human subject to determine the nucleotide present at the polymorphic positions of rs10201482 or rs980286 of the low density lipoprotein related protein 1B (LRP1B) gene; and   identifying that the human subject with one or more G alleles at the polymorphic position of rs10201482 or rs980286 has an increased chance of reaching age 85 without developing cognitive decline.   
     
     
         2 . The method of  claim 1  further comprising assaying for allelic variants selected from the group consisting of rs6732847, rs12053560, and rs6748626 wherein a haplotype of CTG for these allelic variants is indicative of reaching 85 without developing cognitive decline. 
     
     
         3 . The method of  claim 1  further comprising assaying for allelic variants selected from the group consisting of rs13016717, rs1346641, rs10928081, and rs1247461 wherein a haplotype of ATCA for these allelic variants is indicative of reaching 85 without developing cognitive decline. 
     
     
         4 . The method of  claim 1  further comprising assaying for allelic variants selected from the group consisting of rs716000, rs716001, rs10201482, and rs980286 wherein a haplotype of GCGG for these allelic variants is indicative of reaching 85 without developing cognitive decline. 
     
     
         5 . The method of  claim 1  further comprising assaying for allelic variants selected from the group consisting of rs16845065, rs11888460, rs11904038 and rs130087735 wherein a haplotype of GTCG for these allelic variants is indicative of reaching 85 without developing cognitive decline. 
     
     
         6 . The method of  claim 1 , wherein the assaying is carried out by a process selected from the group consisting of direct sequencing, allele-specific probe hybridization, allele-specific primer extension, allele-specific amplification, sequencing, 5′ nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis, and single-stranded conformation polymorphism. 
     
     
         7 . A kit for carrying out the method of  claim 1  comprising at least one oligonucleotide detection reagent, wherein the oligonucleotide detection reagent distinguishes between each of at least two different alleles at the one or more SNP. 
     
     
         8 . The kit of  claim 7 , wherein the detecting is carried out by a process selected from the group consisting of direct sequencing, allele-specific probe hybridization, allele-specific primer extension, allele-specific amplification, sequencing, 5′ nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis, and single-stranded conformation polymorphism. 
     
     
         9 . The kit of  claim 7 , wherein the oligonucleotide detection reagents are immobilized to a substrate. 
     
     
         10 . The kit of  claim 9 , wherein the oligonucleotide detection reagents are arranged in a grid-like pattern on an array. 
     
     
         11 . A computer-implemented system for determining whether a subject will reach 85 without developing cognitive decline comprising means for determining the presence of one or more allelic variants in a gene encoding low density lipoprotein-related protein 1B from a sample obtained from a subject, wherein the one or more allelic variants are selected from the group consisting of rs12474609, rs10201482, and rs980286, and
 means for communicating the detected allelic variants.   
     
     
         12 . The computer implemented system of  claim 11  wherein a haplotype of AGG is indicative of reaching 85 without developing cognitive decline.