Saido's team (Iwata et al
labeled Aβ1-42 into rat hippocampus and found it was metabolized
with a half-life of 39 minutes. They tried many classes of peptide
inhibitors and found that neprilysin type were the only ones that
prevented the breakdown. They then infused one inhibitor (thiorphan)
into normal rat brain and produced rat amyloid deposits in 30 days.
(That beats transgenic models.) We followed this up in our Neuroscience
Letters paper (12 Jan 2001;297:97-100). We found low levels of
neprilysin in plaque prone areas such as the hippocampus and temporal
cortex, and high neprilysin levels in areas such as the striatum,
cerebellum and peripheral organs, which never or rarely ever develop
plaques. Moreover, we found Alzheimer patients had significantly lower
neprilysin levels than normals in vulnerable areas.
Neprilysin is a membrane-bound enzyme highly expressed on axons and
nerve endings of peptide-expressing neurons. Our data help explain...