Detection of APP gene recombinant in human blood plasma

Author:

Mitsunaga Shigeki,Fujito Naoko,Nakaoka Hirofumi,Imazeki Ryoko,Nagata Eiichiro,Inoue Ituro

Abstract

AbstractThe pathogenesis of Alzheimer’s disease (AD) is believed to involve the accumulation of amyloid-β in the brain, which is produced by the sequential cleavage of amyloid precursor protein (APP) by β-secretase and γ-secretase. Recently, analysis of genomic DNA and mRNA from postmortem brain neurons has revealed intra-exonic recombinants of APP (gencDNA), which have been implicated in the accumulation of amyloid-β. In this study, we computationally analyzed publicly available sequence data (SRA) using probe sequences we constructed to screen APP gencDNAs. APP gencDNAs were detected in SRAs constructed from both genomic DNA and RNA obtained from the postmortem brain and in the SRA constructed from plasma cell-free mRNA (cf-mRNA). The SRA constructed from plasma cf-mRNA showed a significant difference in the number of APP gencDNA reads between SAD and NCI: the p-value from the Mann–Whitney U test was 5.14 × 10−6. The transcripts were also found in circulating nucleic acids (CNA) from our plasma samples with NGS analysis. These data indicate that transcripts of APP gencDNA can be detected in blood plasma and suggest the possibility of using them as blood biomarkers for Alzheimer's disease.

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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