Deposition of plaques containing amyloid β (Aβ) peptides is a neuropathological hallmark of Alzheimer's disease (AD). Here we demonstrate that neuronal overexpression of the ε isozyme of PKC decreases Aβ levels, plaque burden, and plaque-associated neuritic dystrophy and reactive astrocytosis in transgenic mice expressing familial AD-mutant forms of the human amyloid precursor protein (APP). Compared with APP singly transgenic mice, APP/PKCε doubly transgenic mice had decreased Aβ levels but showed no evidence for altered cleavage of APP. Instead, PKCε overexpression selectively increased the activity of endothelin-converting enzyme, which degrades Aβ. The activities of other Aβ-degrading enzymes, insulin degrading enzyme and neprilysin, were unchanged. These results indicate that increased neuronal PKCε activity can promote Aβ clearance and reduce AD neuropathology through increased endothelin-converting enzyme activity.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - May 23 2006|
- Alzheimer's disease
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