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Marr, RA, Rockenstein, E, Mukherjee, A, Kindy, MS, Hersh, LB, Gage, FH, Verma, IM and Masliah, E (2003) Neprilysin gene transfer reduces human amyloid pathology in transgenic mice. J. Neurosci. 23:1992-6


The degenerative process of Alzheimer's disease is linked to a shift in the balance between amyloid-beta (Abeta) production, clearance, and degradation. Neprilysin has recently been implicated as a major extracellular Abeta degrading enzyme in the brain. However, there has been no direct demonstration that neprilysin antagonizes the deposition of amyloid-beta in vivo. To address this issue, a lentiviral vector expressing human neprilysin (Lenti-Nep) was tested in transgenic mouse models of amyloidosis. We show that unilateral intracerebral injection of Lenti-Nep reduced amyloid-beta deposits by half relative to the untreated side. Furthermore, Lenti-Nep ameliorated neurodegenerative alterations in the frontal cortex and hippocampus of these transgenic mice. These data further support a role for neprilysin in regulating cerebral amyloid deposition and suggest that gene transfer approaches might have potential for the development of alternative therapies for Alzheimer's disease.




Alzheimer Disease/genetics; Amyloid beta-Peptides/metabolism; Amyloid beta-Protein Precursor/genetics; Amyloidosis/genetics; Amyloidosis/therapy; Animals; Brain/drug effects; Brain/metabolism; Brain/pathology; Cell Line; Disease Models, Animal; Drug Administration Routes; Frontal Lobe/drug effects; Frontal Lobe/metabolism; Frontal Lobe/pathology; Gene Transfer Techniques; Genes, Reporter; Genetic Therapy/methods; Genetic Vectors/administration & dosage; Genetic Vectors/genetics; Hippocampus/drug effects; Hippocampus/metabolism; Hippocampus/pathology; Humans; Kidney/cytology; Kidney/metabolism; Lentivirus/genetics; Mice; Mice, Transgenic; Neprilysin/biosynthesis; Neprilysin/genetics; Neprilysin/pharmacology; Peptide Fragments/metabolism; Plaque, Amyloid/drug effects; Plaque, Amyloid/pathology; Stem Cells/metabolism; Treatment Outcome



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status



GO:0097242: amyloid-beta clearance

ECO:0000314: direct assay evidence used in manual assertion


Seeded From UniProt


See also


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