{
  "abstract": "A hallmark of Alzheimer's disease (AD) is extra-neuronal protein aggregates formed mainly by the amyloid-β peptide (Aβ), that are deposited inside the brain as amyloid plaques. The formation of amyloid plaques requires participation of zinc ions. The 11-Glu-Val-His-His-14 region of Aβ is critical for interaction between Aβ and zinc ions. The engineered peptide Ac-His-Ala-Glu-Glu-NH2 (HAEE) acts as competitive inhibitor of such interactions and suppresses formation of Aβ aggregates in animal models of AD. We sought to develop a reliable method for studying the behavior of the synthetic HAEE peptide in the human blood in preparation for clinical trials of this peptide as a potential anti-amyloid drug for AD. The analytical method to monitor HAEE concentration in blood plasma combines separation by high-performance liquid chromatography and registration on a mass detector of the parent quasi-molecular ion and fragment ions. We discover that HAEE peptide represents a normal endogenous component of human blood plasma. Moreover, the HAEE level has been significantly reduced in patients with a clinical diagnosis of AD (n = 200) as compared with the control participants with no clinical diagnosis of cognitive impairment (n = 150). Deficiency of endogenous HAEE may be considered as a potential blood-based biomarker in the diagnosis of AD, while exogenous synthetic HAEE may serve as a drug in AD-modifying therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Lifemission, LLC , Testovskaia str., 10, pomeshch. 2/6, Moscow 123112 ,",
    "Institute of Biomedical Chemistry, Russian Academy of Sciences , Pogodinskaya str., 10, bld. 8, Moscow 119121 ,",
    "Scientific Centre RTA, LLC , 60-letiya Oktyabrya str., 27/2-40, Moscow 117292 ,",
    "Synthon-Lab Ltd , Bumazhnaya str., 17, office 400, Saint-Petersburg 190020 ,",
    "Burdenko National Medical Research Center for Neurosurgery , 4th Tverskaya-Yamskaya str., 16, Moscow 125047 ,",
    "Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Vavilov str., 32, Moscow 119991 ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Arthur T Kopylov",
      "orcid": "0000-0002-7199-372X"
    },
    {
      "affs": [
        2
      ],
      "name": "Ruslan Yu Yakovlev",
      "orcid": "0000-0003-2655-5154"
    },
    {
      "affs": [
        3
      ],
      "name": "Aleksei V Trukhin",
      "orcid": "0009-0000-4877-1128"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Yuri M Poluektov",
      "orcid": "0000-0002-9710-7490"
    },
    {
      "affs": [
        5
      ],
      "name": "Anastasia A Anashkina",
      "orcid": "0000-0003-1763-300X"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Sergey A Kozin",
      "orcid": "0000-0002-3018-7932"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d7x90cdve687c.bib",
  "cited_by": 0,
  "doi": "10.1093/pnasnexus/pgag320",
  "fulltext_url": "https://europepmc.org/articles/PMC13681328",
  "id": "d7x90cdve687c",
  "issns": [
    "2752-6542"
  ],
  "landing_url": "https://academic.oup.com/pnasnexus/article/doi/10.1093/pnasnexus/pgag320/8935301",
  "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": [
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7223051854",
  "pdf_url": "https://academic.oup.com/pnasnexus/article-pdf/5/10/pgag320/72066862/pgag320.pdf",
  "pmcid": "PMC13681328",
  "pmid": "42903655",
  "published": "2026-10-20",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/d7x90cdve687c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1093/pnasnexus/pgag320",
      "source": "crossref",
      "url": "https://academic.oup.com/pnasnexus/article/doi/10.1093/pnasnexus/pgag320/8935301"
    },
    {
      "first_seen": "2026-10-30T12:19:53Z",
      "native_id": "MED:42903655",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42903655"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Alzheimer's disease research and treatments",
      "subfield": "physiology"
    }
  ],
  "title": "Beyond Alzheimer’s story: How an engineered molecule gained an endogenous essence",
  "title_text": "Beyond Alzheimer’s story: How an engineered molecule gained an endogenous essence",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:53Z",
  "url": "https://research.draconitic.com/paper/d7x90cdve687c",
  "venue": "PNAS Nexus",
  "versions": []
}