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Updated: Jul 9, 2025
Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
Published on: October 17, 2015
Detection of APP gene recombinant in human blood plasma
Shigeki Mitsunaga1, Naoko Fujito2,3, Hirofumi Nakaoka4
1Laboratory of Human Genetics, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka, 411-8540, Japan. smitsunaga@nig.ac.jp.
Abstract:
The 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.
Insights
Researchers found novel Alzheimer's disease (AD) biomarkers in blood plasma. Transcripts of amyloid precursor protein (APP) gencDNA were detected in plasma, suggesting potential for early AD detection.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Alzheimer's disease (AD) pathogenesis involves amyloid-β accumulation.
- Amyloid precursor protein (APP) cleavage by secretases produces amyloid-β.
- Intra-exonic APP recombinants (gencDNA) are implicated in AD.
Purpose of the Study:
- To computationally screen for APP gencDNAs in publicly available sequence data.
- To investigate the presence of APP gencDNA transcripts in blood plasma.
- To explore the potential of APP gencDNA as a blood biomarker for Alzheimer's disease.
Main Methods:
- Computational analysis of Sequence Read Archive (SRA) data.
- Screening for APP gencDNAs using constructed probe sequences.
- Next-generation sequencing (NGS) analysis of plasma cell-free mRNA (cf-mRNA) and circulating nucleic acids (CNA).
Main Results:
- APP gencDNAs were detected in SRA data from postmortem brain (genomic DNA and RNA) and plasma cf-mRNA.
- A significant difference in APP gencDNA reads was observed between SAD and NCI in plasma cf-mRNA (p < 5.14 × 10⁻⁶).
- APP gencDNA transcripts were identified in circulating nucleic acids from plasma samples.
Conclusions:
- APP gencDNA transcripts are detectable in blood plasma.
- These transcripts show potential as novel blood biomarkers for Alzheimer's disease.
- Further research may validate APP gencDNA for early AD diagnosis and monitoring.
