Beyond Alzheimer’s story: How an engineered molecule gained an endogenous essence
6 affiliations
- 1Lifemission, LLC , Testovskaia str., 10, pomeshch. 2/6, Moscow 123112 ,
- 2Institute of Biomedical Chemistry, Russian Academy of Sciences , Pogodinskaya str., 10, bld. 8, Moscow 119121 ,
- 3Scientific Centre RTA, LLC , 60-letiya Oktyabrya str., 27/2-40, Moscow 117292 ,
- 4Synthon-Lab Ltd , Bumazhnaya str., 17, office 400, Saint-Petersburg 190020 ,
- 5Burdenko National Medical Research Center for Neurosurgery , 4th Tverskaya-Yamskaya str., 16, Moscow 125047 ,
- 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Vavilov str., 32, Moscow 119991 ,
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.
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BibTeX
@article{kopylov2026beyond,
title = {{Beyond Alzheimer’s story: How an engineered molecule gained an endogenous essence}},
author = {Arthur T Kopylov and Ruslan Yu Yakovlev and Aleksei V Trukhin and Yuri M Poluektov and Anastasia A Anashkina and Sergey A Kozin},
journal = {PNAS Nexus},
year = {2026},
month = oct,
doi = {10.1093/pnasnexus/pgag320},
url = {https://academic.oup.com/pnasnexus/article/doi/10.1093/pnasnexus/pgag320/8935301},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Beyond Alzheimer’s story: How an engineered molecule gained an endogenous essence
AU - Arthur T Kopylov
AU - Ruslan Yu Yakovlev
AU - Aleksei V Trukhin
AU - Yuri M Poluektov
AU - Anastasia A Anashkina
AU - Sergey A Kozin
PY - 2026
DA - 2026/10/20
JO - PNAS Nexus
DO - 10.1093/pnasnexus/pgag320
UR - https://academic.oup.com/pnasnexus/article/doi/10.1093/pnasnexus/pgag320/8935301
AB - 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.
SN - 2752-6542
ER -