Engineered Peptide that Suppresses Amyloid-β Aggregation Found to Exist in the Body
Researchers here relate an interesting story: they designed and synthesized a small peptide that is intended to interfere with an interaction between amyloid-β and zinc ions, with the aim of suppressing a necessary part of the process of amyloid-β aggregation. This amyloid-β aggregation, proceeding slowly over years, is thought to be the causative mechanism in Alzheimer's disease. The researchers then discovered that this peptide already exists in the body, and is in fact reduced in level in Alzheimer's patients.
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.