Presynaptic Localization of Neprilysin Contributes to Efficient Clearance of Amyloid-β Peptide in Mouse Brain
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<jats:p>A local increase in amyloid-β peptide (Aβ) is closely associated with synaptic dysfunction in the brain in Alzheimer's disease. Here, we report on the catabolic mechanism of Aβ at the presynaptic sites. Neprilysin, an Aβ-degrading enzyme, expressed by recombinant adeno-associated viral vector-mediated gene transfer, was axonally transported to presynaptic sites through afferent projections of neuronal circuits. This gene transfer abolished the increase in Aβ levels in the hippocampal formations of neprilysin-deficient mice and also reduced the increase in young mutant amyloid precursor protein transgenic mice. In the latter case, Aβ levels in the hippocampal formation contralateral to the vector-injected side were also significantly reduced as a result of transport of neprilysin from the ipsilateral side, and in both sides soluble Aβ was degraded more efficiently than insoluble Aβ. Furthermore, amyloid deposition in aged mutant amyloid precursor protein transgenic mice was remarkably decelerated. Thus, presynaptic neprilysin has been demonstrated to degrade Aβ efficiently and to retard development of amyloid pathology.</jats:p>
収録刊行物
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- The Journal of Neuroscience
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The Journal of Neuroscience 24 (4), 991-998, 2004-01-28
Society for Neuroscience
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詳細情報 詳細情報について
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- CRID
- 1360292621053280768
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- NII論文ID
- 30010122219
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- ISSN
- 15292401
- 02706474
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- データソース種別
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