Research ArticleAlzheimer’s Disease

Gene Transfer of Human Apoe Isoforms Results in Differential Modulation of Amyloid Deposition and Neurotoxicity in Mouse Brain

Science Translational Medicine  20 Nov 2013:
Vol. 5, Issue 212, pp. 212ra161
DOI: 10.1126/scitranslmed.3007000

You are currently viewing the editor's summary.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.

Variants and Risk in Alzheimer’s Disease

Certain genes help to determine the chance that someone will develop Alzheimer’s disease (AD). In the case of the APOE gene, one form of the gene increases the risk of developing AD, whereas another form decreases the risk. Hudry et al. use a transgenic mouse model of AD and advanced microscopy techniques to examine one mechanism that might help to explain how these different APOE isoforms affect the risk of developing AD. The authors used gene therapy to deliver the APOE4 high-risk human gene variant or the APOE2, protective human gene variant to transgenic mice with amyloid plaques, a pathological characteristic of AD. Introduction of the APOE4 variant increased the rate at which amyloid plaques developed and increased plaque-associated damage to brain neurons. In contrast, the APOE2 variant did the opposite with shrinking of some amyloid plaques and plaque-associated damage in the brains of mice receiving human APOE2. These results confirm a major role for APOE4 in amyloid deposition and may help to guide development of therapies aimed at mitigating APOE4 risk or enhancing APOE2-mediated protection.