Document Type

Journal Article

Publisher

PLOS

Faculty

Faculty of Computing, Health and Science

School

School of Exercise, Biomedical and Health Sciences / Centre of Excellence for Alzheimer's Disease Research and Care

RAS ID

16876

Comments

Drummond, E.S., Muhling, J., Martins, R.N., Wijaya, L.K., Ehlert, E.M., & Harvey, A.R. (2013). Pathology associated with AAV mediated expression of beta amyloid or C100 in adult mouse hippocampus and cerebellum. PLoS ONE, 8(3), e59166. Available here

Abstract

Accumulation of beta amyloid (Ab) in the brain is a primary feature of Alzheimer’s disease (AD) but the exact molecular mechanisms by which Ab 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 Ab40- GFP, Ab42-GFP, C100-GFP or C100V717F-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 Ab protein after injection with AAV vectors, injection of rAAV2-Ab42-GFP and rAAV2- C100V717F-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-Ab40-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 Ab and C100 is a powerful technique with which to examine the direct in vivo consequences of Ab 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.

DOI

10.1371/journal.pone.0059166

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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