Naturally occurring blood molecule linked to lower Alzheimer’s risk

Researchers developed a drug for Alzheimer’s disease, and then discovered that the molecule already exists in human blood, and is found in lower levels in cognitively impaired people. Now the authors are exploring the peptide as a biomarker as well as a treatment.

Sergey A. Kozin and colleagues designed a peptide to interfere with the growth of amyloid-β peptide (Aβ) plaques in the brain. Preventing the formation of such plaques has been proposed as a way to prevent Alzheimer’s disease or treat it in its earlier stages, in part because Aβ plaque formation is believed to precede and potentially cause the spread of toxic tau protein. Specifically, the authors sought to disrupt abnormal interactions between Aβ and zinc ions, an interaction thought to be key to the plaque formation process.

The tetrapeptide Ac-His-Ala-Glu-Glu-NH2 (HAEE) blocks the primary zinc-binding center in Aβ monomers. In the process of testing HAEE’s suitability as a drug, the authors not only obtained promising results in mice, but unexpectedly discovered that an identical peptide was already circulating in human blood. In effect, the authors had reverse-engineered a molecule that evolution had already produced. Furthermore, levels of HAEE correlate with disease status, while Aβ levels are the same in people with Alzheimer’s disease and healthy people. According to the authors, HAEE deficiency may be a cause of Alzheimer’s disease, and HAEE blood concentration may be a useful biomarker to help diagnose the disease.