{
  "abstract": "Cancer and Alzheimer’s disease (AD) are common age-associated disorders characterized by contrasting cellular outcomes, yet epidemiological studies repeatedly report an apparent, modest bidirectional inverse association between cancer and dementia, including AD. This Mini Review examines the extent to which this pattern reflects biological antagonism versus competing mortality, diagnostic bias, survivor selection, and treatment exposure. Breast and prostate cancers are considered as endocrine models because estrogen- and androgen-receptor signaling supports tumor growth while also regulating neuronal metabolism, mitochondrial function, vascular homeostasis, and inflammation. Population studies show heterogeneous neurological associations for breast cancer hormone-modulating therapy and prostate cancer androgen-deprivation therapy, emphasizing the need to distinguish tumor biology from systemic endocrine treatment. Mechanistically, cancer and AD engage overlapping metabolic pathways, including insulin/IGF–PI3K–AKT, mTOR, and AMPK; cell-fate programs involving cell-cycle control and senescence; and proteostatic systems involving molecular chaperones and autophagy–lysosomal function. These networks produce divergent outcomes: proliferative and proteotoxic adaptation in tumors versus energetic failure, impaired proteostasis, and neuronal degeneration in AD. Protein self-assembly provides an additional, context-dependent connection: amyloidogenic proteins can modify cancer-cell fitness, while recent preclinical evidence identifies a tumor-derived cystatin C–TREM2 pathway that enhances cerebral Aβ clearance. Whether these mechanisms contribute to human cancer–AD inverse comorbidity remains unproven. The observed cancer–AD inverse comorbidity therefore likely reflects interacting epidemiological, endocrine, metabolic, proteostatic, and protein-assembly mechanisms rather than a single causal pathway. Treatment-aware longitudinal studies incorporating AD biomarkers and physiologically relevant models are needed to distinguish genuine biological antagonism from observational bias.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Endocrinology and Diabetes, Department of Pediatrics, School of Medicine, Stanford University",
    "Department of Biomedical Engineering and Chemical Engineering, The University of Texas at San Antonio"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yanxian Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Lijin Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Jialun Wei"
    },
    {
      "affs": [
        1
      ],
      "name": "Nazmul Shuzan"
    },
    {
      "affs": [
        1
      ],
      "name": "Jie Zheng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5nvb8kna3eckw.bib",
  "cited_by": 0,
  "doi": "10.3389/fendo.2026.1992522",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13725551/?tool=EBI",
  "id": "5nvb8kna3eckw",
  "issns": [
    "1664-2392"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1992522/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Mini Review"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
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  "openalex": "W7222949328",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13725551/pdf/?tool=EBI",
  "pmcid": "PMC13725551",
  "pmid": "42974248",
  "published": "2026-10-19",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/5nvb8kna3eckw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:20Z",
      "native_id": "10.3389/fendo.2026.1992522",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1992522/full"
    },
    {
      "first_seen": "2026-11-03T15:20:50Z",
      "native_id": "PMC:PMC13725551",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13725551"
    },
    {
      "first_seen": "2026-11-04T12:23:54Z",
      "native_id": "PMC13725551",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fendo.2026.1992522"
    },
    {
      "first_seen": "2026-11-04T15:20:48Z",
      "native_id": "MED:42974248",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42974248"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Alzheimer's disease research and treatments",
      "subfield": "physiology"
    }
  ],
  "title": "Cancer–Alzheimer inverse comorbidity from epidemiology to protein self-assembly",
  "title_text": "Cancer–Alzheimer inverse comorbidity from epidemiology to protein self-assembly",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:21:46Z",
  "url": "https://research.draconitic.com/paper/5nvb8kna3eckw",
  "venue": "Frontiers in Endocrinology",
  "versions": []
}