科研之友
微信
新浪微博
Facebook
分享链接
摘要
The apolipoprotein E (APOE) epsilon 4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). The influence of apoE on amyloid beta (A beta) accumulation may be the major mechanism by which apoE affects AD. ApoE interacts with A. and facilitates A beta fibrillogenesis in vitro. In addition, apoE is one of the protein components in plaques. We hypothesized that certain anti-apoE antibodies, similar to certain anti-A beta antibodies, may have antiamyloidogenic effects by binding to apoE in the plaques and activating microglia-mediated amyloid clearance. To test this hypothesis, we developed several monoclonal anti-apoE antibodies. Among them, we administered HJ6.3 antibody intraperitoneally to 4-mo-old male APPswe/PS1 Delta E9 mice weekly for 14 wk. HJ6.3 dramatically decreased amyloid deposition by 60-80% and significantly reduced insoluble A beta 40 and A beta 42 levels. Short-term treatment with HJ6.3 resulted in strong changes in microglial responses around A beta plaques. Collectively, these results suggest that anti-apoE immunization may represent a novel AD therapeutic strategy and that other proteins involved in A. binding and aggregation might also be a target for immunotherapy. Our data also have important broader implications for other amyloidosis. Immunotherapy to proteins tightly associated with misfolded proteins might open up a new treatment option for many protein misfolding diseases.
- 出版日期2012-11-19
