{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:47:22Z","timestamp":1792500442821,"version":"4.5.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lifemission"},{"DOI":"10.13039\/100023970","name":"LLC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100023970","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A hallmark of Alzheimer's disease (AD) is extra-neuronal protein aggregates formed mainly by the amyloid-\u03b2 peptide (A\u03b2), 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 A\u03b2 is critical for interaction between A\u03b2 and zinc ions. The engineered peptide Ac-His-Ala-Glu-Glu-NH2 (HAEE) acts as competitive inhibitor of such interactions and suppresses formation of A\u03b2 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.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgag320","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:01:16Z","timestamp":1792497676000},"source":"Crossref","is-referenced-by-count":0,"title":["Beyond Alzheimer\u2019s story: How an engineered molecule gained an endogenous essence"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7199-372X","authenticated-orcid":false,"given":"Arthur T","family":"Kopylov","sequence":"first","affiliation":[{"name":"Lifemission, LLC , Testovskaia str., 10, pomeshch. 2\/6, Moscow 123112 ,","place":["Russia"]},{"name":"Institute of Biomedical Chemistry, Russian Academy of Sciences , Pogodinskaya str., 10, bld. 8, Moscow 119121 ,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2655-5154","authenticated-orcid":false,"given":"Ruslan Yu","family":"Yakovlev","sequence":"additional","affiliation":[{"name":"Scientific Centre RTA, LLC , 60-letiya Oktyabrya str., 27\/2-40, Moscow 117292 ,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4877-1128","authenticated-orcid":false,"given":"Aleksei V","family":"Trukhin","sequence":"additional","affiliation":[{"name":"Synthon-Lab Ltd , Bumazhnaya str., 17, office 400, Saint-Petersburg 190020 ,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9710-7490","authenticated-orcid":false,"given":"Yuri M","family":"Poluektov","sequence":"additional","affiliation":[{"name":"Burdenko National Medical Research Center for Neurosurgery , 4th Tverskaya-Yamskaya str., 16, Moscow 125047 ,","place":["Russia"]},{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Vavilov str., 32, Moscow 119991 ,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1763-300X","authenticated-orcid":false,"given":"Anastasia A","family":"Anashkina","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Vavilov str., 32, Moscow 119991 ,","place":["Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3018-7932","authenticated-orcid":false,"given":"Sergey A","family":"Kozin","sequence":"additional","affiliation":[{"name":"Lifemission, LLC , Testovskaia str., 10, pomeshch. 2\/6, Moscow 123112 ,","place":["Russia"]},{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Vavilov str., 32, Moscow 119991 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Nexus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/5\/10\/pgag320\/72066862\/pgag320.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/5\/10\/pgag320\/72066862\/pgag320.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:01:20Z","timestamp":1792497680000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article\/doi\/10.1093\/pnasnexus\/pgag320\/8935301"}},"subtitle":[],"editor":[{"given":"Andrey","family":"Abramov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":32,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,9,30]]}},"URL":"https:\/\/doi.org\/10.1093\/pnasnexus\/pgag320","relation":{},"ISSN":["2752-6542"],"issn-type":[{"value":"2752-6542","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10]]},"published":{"date-parts":[[2026,9,30]]},"article-number":"pgag320"}}