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Global brain delivery of neprilysin gene by intravascular administration of AAV vector in mice

Iwata, N, Sekiguchi, M, Hattori, Y, Takahashi, A, Asai, M, Ji, B, Higuchi, M, Staufenbiel, M, Muramatsu, S and Saido, TC (2013) Global brain delivery of neprilysin gene by intravascular administration of AAV vector in mice. Scientific Reports.


Accumulation of amyloid-beta peptide (A beta) in the brain is closely associated with cognitive decline in Alzheimer's disease (AD). Stereotaxic infusion of neprilysin-encoding viral vectors into the hippocampus has been shown to decreaseA beta in AD-model mice, but more efficient and global delivery is necessary to treat the broadly distributed burden in AD. Here we developed an adeno-associated virus (AAV) vector capable of providing neuronal gene expression throughout the brains after peripheral administration. A single intracardiac administration of the vector carrying neprilysin gene in AD-model mice elevated neprilysin activity broadly in the brain, and reduced A beta oligomers, with concurrent alleviation of abnormal learning and memory function and improvement of amyloid burden. The exogenous neprilysin was localized mainly in endosomes, thereby effectively excluding A beta oligomers from the brain. AAV vector-mediated gene transfer may provide a therapeutic strategy for neurodegenerative diseases, where global transduction of a therapeutic gene into the brain is necessary

Item Type: Article
Additional Information: pubid: 105 nvp_institute: NIBR contributor_address: [Iwata, Nobuhisa; Sekiguchi, Misaki; Saido, Takaomi C.] RIKEN, Brain Sci Inst, Lab Proteolyt Neurosci, Wako, Saitama 3510198, Japan. [Iwata, Nobuhisa; Hattori, Yoshino; Takahashi, Akane; Asai, Masashi] Nagasaki Univ, Grad Sch Biomed Sci, Dept Mol Med Sci, Lab Mol Biol & Biotechnol, Nagasaki 8528521, Japan. [Ji, Bin; Higuchi, Makoto] Natl Inst Radiol Sci, Mol Imaging Ctr, Inage Ku, Chiba 2638555, Japan. [Staufenbiel, Matthias] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. [Muramatsu, Shin-ichi] Jichi Med Univ, Dept Med, Div Neurol, Shimotsuke, Tochigi 3290498, Japan.
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13


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