The enzyme neprilysin-capable of degrading Aβ42 peptide-is a new player in the Alzheimer's disease mystery. Writing in Neuroscience Letters, Patrick McGeer's group at the University of British Columbia adds critical circumstantial evidence that places neprilysin at the scene of neurodegeneration. Neprilysin (alias neural endopeptidase, EC188.8.131.52, enkephalinase, CD10, or common acute lymphblastic leukemia antigen [CALLA]) cleaves enkephalins, endorphins, substance P, and other small peptides throughout the body. Recent animal data show that when neprilysin is inhibited, amyloid deposits can build up quickly. The suggestion has been made that compromised neprilysin-mediated scavenging of Aβ is important to the final pathology of Alzheimer's.
McGeer and colleagues compared neprilysin mRNA and protein levels in postmortem human brain and other organs of AD and control cases. Within both study groups, the hippocampus and temporal gyrus, areas susceptible to plaques, showed particularly low levels of neprilysin mRNA. Conversely, the caudate and peripheral organs that are resistant to plaque formation had the highest levels of neprilysin mRNA. Compared to controls, neprilysin mRNA levels in AD brains were much lower in hippocampus and midtemporal gyrus, but not in other areas. Similar patterns was found for the protein product.
"If the human brain depends upon neprilysin as the main enzyme to break down Aβ, then the data reported here would help to explain why areas such as the hippocampus and temporal gyrus are highly vulnerable to plaque formation," write the authors. "They would also help to explain why Aβ deposits do not appear in peripheral organs but are confined to restricted regions of the brain."—Hakon Heimer
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- Yasojima K, Akiyama H, McGeer EG, McGeer PL. Reduced neprilysin in high plaque areas of Alzheimer brain: a possible relationship to deficient degradation of beta-amyloid peptide. Neurosci Lett. 2001 Jan 12;297(2):97-100. PubMed.