Detection of APP gene recombinant in human blood plasma.

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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.", "claims": [{"id": "claim-method", "statement": "When each read count of APP gencDNA read was normalized by dividing the read count of the housekeeping gene GAPDH, significant differences were observed between SAD and NCI: p-value by the Mann–Whitney U test was 5.14 × 10−6 (Fig. 2a).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38066066", "locator": "sections[5] \"Comparison of the number of APP gencDNA reads in an SRA from plasma cf-mRNA\" paragraph 2", "quote": "When each read count of APP gencDNA read was normalized by dividing the read count of the housekeeping gene GAPDH, significant differences were observed between SAD and NCI: p-value by the Mann–Whitney U test was 5.14 × 10−6 (Fig. 2a)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and analysed during the current study are available with links to BioProject accession number PRJDB16023 in the DDBJ BioProject database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38066066", "locator": "sections[16] \"Data availability\" paragraph 2", "quote": "The datasets generated and analysed during the current study are available with links to BioProject accession number PRJDB16023 in the DDBJ BioProject database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "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.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38066066", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "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."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "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.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38066066"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_unresolved", "description": "The GEO series accession resolves and its sample accessions are listed. 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