{
  "abstract": "Amyloid[beta]; (A[beta];) plaques are a hallmark of Alzheimer[prime]s disease (AD). A human cellular neuronal model that recaptures A[beta];-induced pathology is critical for advancing AD research. However, comprehensive proteomic profiling of A[beta];-induced cellular model remains elusive. In this study, we investigated the proteomic changes in induced pluripotent stem cell (iPSC)-derived neurons (iNs) exposed to synthetic A[beta]; (1-42) peptides (A[beta];42A) to improve our understanding of the cellular responses of A[beta]; aggregates and to establish a human-related platform for AD research. A[beta];42A formed extracellular aggregates around neuronal soma and neurites, impaired neurite outgrowth, and induced the expression of multiple AD-associated genes, such as APOE, BACE1, ADAM10. To define the molecular landscape of A[beta];-induced neuronal dysfunction, we performed proteomic analyses of whole-cell lysates as well as soma- and neurite-enriched fractions. Proteomic profiling revealed extensive gene alterations in pathways associated with synaptic function, neuronal maintenance, and AD pathogenesis, such as the upregulation of APOE. Importantly, the A[beta];42A-iNs system recapitulated molecular signatures observed in AD brain tissue and cerebrospinal fluid. Representative protein changes, including APOE upregulation and its colocalization with A[beta]; aggregates, were further validated in postmortem human AD brain tissue. Together, these findings manifest that the A[beta];42A-iNs system reproduces multiple cellular and molecular features of AD and exhibits strongly consensus with clinical observations. It provides a valuable platform for investigating A[beta];-driven neurodegeneration and for the discovery of therapeutic targets for AD.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "name": "B. Jin"
    },
    {
      "name": "Z. Li"
    },
    {
      "name": "Y. Hao"
    },
    {
      "name": "I. Kowal"
    },
    {
      "name": "J. Epstein"
    },
    {
      "name": "M. Santiana"
    },
    {
      "name": "C. Weller"
    },
    {
      "name": "M. A. Nalls"
    },
    {
      "name": "D. Tao"
    },
    {
      "name": "S. Fang"
    },
    {
      "name": "P. Narayan"
    },
    {
      "name": "A. B. Singleton"
    },
    {
      "name": "K. V. Keuren-Jensen"
    },
    {
      "name": "L. Ferrucci"
    },
    {
      "name": "M. E. Ward"
    },
    {
      "name": "M. R. Cookson"
    },
    {
      "name": "E. Lara"
    },
    {
      "name": "V. H. Ryan"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. A. Qi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fgdztyaq165rt.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.20.753014",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.20.753014v1.full",
  "id": "fgdztyaq165rt",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.20.753014v1",
  "language": null,
  "licence": "CC0-1.0",
  "licence_label": "CC0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/publicdomain/zero/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7214396160",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.20.753014v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-20",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fgdztyaq165rt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:35Z",
      "native_id": "10.64898/2026.09.20.753014",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.20.753014v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Profiling of Aggregated Amyloid β42-induced Proteomic Alterations in KOLF2.1J Induced Pluripotent Stem Cell-derived Neurons",
  "title_text": "Profiling of Aggregated Amyloid β42-induced Proteomic Alterations in KOLF2.1J Induced Pluripotent Stem Cell-derived Neurons",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:35Z",
  "url": "https://research.draconitic.com/paper/fgdztyaq165rt",
  "venue": "bioRxiv",
  "versions": []
}