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bioRxiv · 10.1101/2025.09.22.677901

Beyond Alzheimer's story: how an engineered molecule gained an endogenous essence

Kopylov, A. T.·Yakovlev, R. Y.·Trukhin, A. V.·Poluektov, Y. M.·Anastasia, A. A.·Kozin, S. A.
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Abstract

A hallmark of Alzheimers disease (AD) is extra-neuronal protein aggregates formed mainly by the amyloid-{beta} peptide (A{beta}), that are deposited inside the brain as amyloid plaques. The engineered peptide Ac-His-Ala-Glu-Glu-NH2 (HAEE) suppresses the formation of amyloid plaques in vivo and is being tested as an anti-amyloid drug candidate. Here, by using a quantitative mass-spectrometry method 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). Thus, endogenous HAEE may be considered as a potential blood-based biomarker in the diagnosis of Alzheimers disease, while exogenous HAEE may serve as a drug in AD-modifying therapy.

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Kopylov, A. T., Yakovlev, R. Y., Trukhin, A. V., Poluektov, Y. M., Anastasia, A. A., Kozin, S. A.. 2025-09-22. Beyond Alzheimer's story: how an engineered molecule gained an endogenous essence. https://doi.org/10.1101/2025.09.22.677901

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