RT Journal Article
SR Electronic
T1 Presynaptic Localization of Neprilysin Contributes to Efficient Clearance of Amyloid-β Peptide in Mouse Brain
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 991
OP 998
DO 10.1523/JNEUROSCI.4792-03.2004
VO 24
IS 4
A1 Nobuhisa Iwata
A1 Hiroaki Mizukami
A1 Keiro Shirotani
A1 Yoshie Takaki
A1 Shin-ichi Muramatsu
A1 Bao Lu
A1 Norma P. Gerard
A1 Craig Gerard
A1 Keiya Ozawa
A1 Takaomi C. Saido
YR 2004
UL http://www.jneurosci.org/content/24/4/991.abstract
AB 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.