While much Alzheimer's research has focused on mechanisms that result in the formation of amyloid plaques, a growing body of evidence indicates that processes that break down Aβ are just as important, and may offer novel targets for therapy. A paper by Iwata, et al., appearing in today's Science, presents in vivo evidence that the Aβ-degrading peptidase neprilysin plays a role in regulating Aβ levels. The researchers "knocked out" the neprilysin gene in mice. The lack of the gene apparently has no determinental effects on the mice. The researchers injected Aβ peptide into the hippocampus, then 30 minutes later measured Aβ levels in the brain tissue. In normal mice with a working neprilysin gene, 70 percent to 80 percent of the injected Aβ was degraded, but in mice lacking one copy of neprilysin, substantially less was degraded, and in mice lacking both copies of the gene, the Aβ remained undegraded. The authors speculate that an age-related decline in neprilysin could result in accumulation of Aβ to pathogenic levels, and that a drug that boosts neprilysin levels might be therapeutic. They also note that the neprilysin gene lies on a stretch of chromosome 3 that has been reported to be associated with an elevated risk of late-onset Alzheimer's.
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