%0 Journal Article %T Peripheral Delivery of a CNS Targeted, Metalo-Protease Reduces A¦Â Toxicity in a Mouse Model of Alzheimer's Disease %A Brian Spencer %A Robert A. Marr %A Ryan Gindi %A Rewati Potkar %A Sarah Michael %A Anthony Adame %A Edward Rockenstein %A Inder M. Verma %A Eliezer Masliah %J PLOS ONE %D 2012 %I Public Library of Science (PLoS) %R 10.1371/journal.pone.0016575 %X Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid ¦Â-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of A¦Â, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD. %U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016575