title: Pathology associated with AAV mediated expression of beta amyloid or C100 in adult mouse hippocampus and cerebellum.
abstract: Accumulation of beta amyloid (Aβ) in the brain is a primary feature of Alzheimer's disease (AD) but the exact molecular mechanisms by which Aβ exerts its toxic actions are not yet entirely clear. We documented pathological changes 3 and 6 months after localised injection of recombinant, bi-cistronic adeno-associated viral vectors (rAAV2) expressing human Aβ40-GFP, Aβ42-GFP, C100-GFP or C100(V717F)-GFP into the hippocampus and cerebellum of 8 week old male mice. Injection of all rAAV2 vectors resulted in wide-spread transduction within the hippocampus and cerebellum, as shown by expression of transgene mRNA and GFP protein. Despite the lack of accumulation of Aβ protein after injection with AAV vectors, injection of rAAV2-Aβ42-GFP and rAAV2- C100(V717F)-GFP into the hippocampus resulted in significantly increased microgliosis and altered permeability of the blood brain barrier, the latter revealed by high levels of immunoglobulin G (IgG) around the injection site and the presence of IgG positive cells. In comparison, injection of rAAV2-Aβ40-GFP and rAAV2-C100-GFP into the hippocampus resulted in substantially less neuropathology. Injection of rAAV2 vectors into the cerebellum resulted in similar types of pathological changes, but to a lesser degree. The use of viral vectors to express different types of Aβ and C100 is a powerful technique with which to examine the direct in vivo consequences of Aβ expression in different regions of the mature nervous system and will allow experimentation and analysis of pathological AD-like changes in a broader range of species other than mouse.
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Western Australia, Australia. E.Drummond@murdoch.edu.au
authors.forename: Eleanor S
authors.initials: ES
authors.lastname: Drummond
authors.forename: Jill
authors.initials: J
authors.lastname: Muhling
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.forename: Linda K
authors.initials: LK
authors.lastname: Wijaya
authors.forename: Erich M
authors.initials: EM
authors.lastname: Ehlert
authors.forename: Alan R
authors.initials: AR
authors.lastname: Harvey
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology*; D000229:Dependovirus / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics*; D006367:HeLa Cells; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016716:PC12 Cells
chemical_list: D016229:Amyloid beta-Peptides