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

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.