Skip to main content
U.S. flag

An official website of the United States government

Peripheral delivery of a CNS targeted, metalo-protease reduces Aβ toxicity in a mouse model of Alzheimer's disease


Year of Publication:
Contact PI Name:
Eliezer Masliah
Contact PI Affiliation:
University of California San Diego, La Jolla, California, USA
Brian Spencer, Robert A. Marr, Ryan Gindi, Rewati Potkar, Sarah Michael, Anthony Adame, Edward Rockenstein, Inder M. Verma
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Study Goal and Principal Findings:

Recently, a novel approach was developed for delivering therapeutic proteins to neurons of the CNS by targeting passage across the BBB. Fusion of the Apolipoprotein B (ApoB) low-density lipoprotein (LDL) receptor-binding domain to a targeted protein allows active transport of the protein across the BBB to the CNS. The fusion proteins can be taken up by neurons and astrocytes across the whole brain. To investigate the potential therapeutic value of a secreted neprilysin (NEP) targeted to the CNS,  the authors generated lentivirus vectors expressing either the wildtype NEP, a secreted form of the NEP or a secreted form of the NEP fused with the LDL-receptor binding domain of ApoB and injected them intra-peritoneally in an amyloid protein precursor (APP) transgenic (tg) model of AD-like pathology.  Results showed that ApoBSecNEP was efficiently trafficked into the CNS and reduced levels of Aβ and synaptic alterations in the brains of mice. In addition, we observed improvements in learning and memory just 1 month after vector delivery. These results suggest a novel, and improved approach for delivery of an Aβ degrading enzyme and other neuroactive peptides to the CNS for treatment of AD.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Peptide
Therapeutic Agent:
Therapeutic Target:
beta Amyloid Peptide

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Morris Water Maze
beta Amyloid Load
Activated Microglia
Brain-beta Amyloid Deposits
Intracellular beta Amyloid Peptide
Synaptic Markers
Apolipoprotein B-Secreted Neprilysin
Brain-beta Amyloid Peptide 42
Postsynaptic Density Protein 95 (PSD95)
Synaptosome Associated Protein 25 (SNAP25)
Amyloid Precursor Protein (APP)
Soluble Amyloid Precursor Protein (sAPP)
Apolipoprotein B-Secreted Neprilysin
Cell Biology
Neuroprotection-Amyloid Neurotoxicity