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Angiotensin-converting enzyme converts amyloid beta-protein 1-42 (Abeta(1-42)) to Abeta(1-40), and its inhibition enhances brain Abeta deposition



Angiotensin-converting enzyme converts amyloid beta-protein 1-42 (Abeta(1-42)) to Abeta(1-40), and its inhibition enhances brain Abeta deposition



Journal of Neuroscience 27(32): 8628-8635



The abnormal deposition of the amyloid beta-protein (A beta) in the brain appears crucial to the pathogenesis of Alzheimer's disease (AD). Recent studies have suggested that highly amyloidogenic A beta(1-42) is a cause of neuronal damage leading to AD pathogenesis and that monomeric A beta(1-40) has less neurotoxicity than A beta(1-42). We found that mouse and human brain homogenates exhibit an enzyme activity converting A beta(1-42) to A beta(1-40) and that the major part of this converting activity is mediated by the angiotensin-converting enzyme (ACE). Purified human ACE converts A beta(1-42) to A beta(1-40) as well as decreases A beta(1-42)/ A beta(1-40) ratio and degrades A beta(1-42) and A beta(1-40). Importantly, the treatment of Tg2576 mice with an ACE inhibitor, captopril, promotes predominant A beta(1-42) deposition in the brain, suggesting that ACE regulates A beta(1-42)/A beta(1-40) ratio in vivo by converting secreted A beta(1-42) to A beta(1-40) and degrading A beta s. The upregulation of ACE activity can be a novel therapeutic strategy for AD.

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Accession: 051549616

Download citation: RISBibTeXText

PMID: 17687040

DOI: 10.1523/JNEUROSCI.1549-07.2007


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