{
  "abstract": "Single-nucleus RNA-seq (snRNA-seq) studies of Alzheimer's disease (AD) routinely filter nuclei by mitochondrial percentage (%MT), yet whether these reads carry information about cognition is rarely examined. In the Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD) microglia snRNA-seq dataset, a transcriptome-wide screen identified a module of MT-CO3 and eight co-expressed mitochondrial genes. Three microglial populations were analyzed: PVM_3, M4 (Mic.13-like), and PVM_1, with a housekeeping-gene control. The CEP-IP pipeline with a copula monotone recovery filter (CMRF) used per-cell Spearman and Kendall scores, an inflection point (IP), and a cross-validated copula space boundary to isolate MT-CO3 Module cells. The donor percentage of Module cells past the IP (Module post-IP%) was significantly associated with worse cognition (MMSE and CASI; FDR<0.05) in all three populations. In PVM_3 and M4, these associations remained significant after adjustment for tissue quality, plaque burden, tangle burden, and contamination, and after doublet removal. PVM_3 and M4 Module post-IP% repeated in each donor's regions beyond chance, and no per-cell %MT cutoff reproduced the Module cells. In two external datasets without cognitive scores, the MT-CO3 module and its IP replicated. However, at the donor level, Module post-IP% could not be separated from mean %MT, and the source of the mitochondrial transcripts (e.g., retained cytoplasm or a true change in mitochondrial content) remains unresolved. Routine %MT filtering in AD snRNA-seq may therefore remove cells that carry information about cognition. The R package cepip, the pipeline code, and a software container that reproduced the findings are publicly available.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kah Keng Wong",
      "orcid": "0000-0001-7359-6202"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/de6ett8qy3caf.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.22.761284",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761284v1.full",
  "id": "de6ett8qy3caf",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761284v1",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7223388333",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761284v1.full.pdf",
  "pmcid": "PMC13733723",
  "pmid": "42990177",
  "published": "2026-10-22",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/de6ett8qy3caf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:48Z",
      "native_id": "10.64898/2026.10.22.761284",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761284v2"
    },
    {
      "first_seen": "2026-11-08T12:23:26Z",
      "native_id": "PMC13733723",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.22.761284"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "CEP-IP with CMRF in SEA-AD Microglia: A Mitochondrial Co-expression Module Linked to Cognition",
  "title_text": "CEP-IP with CMRF in SEA-AD Microglia: A Mitochondrial Co-expression Module Linked to Cognition",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:26Z",
  "url": "https://research.draconitic.com/paper/de6ett8qy3caf",
  "venue": "bioRxiv",
  "versions": []
}