| First Author | Takeda S | Year | 2013 |
| Journal | FASEB J | Volume | 27 |
| Issue | 8 | Pages | 3239-48 |
| PubMed ID | 23640054 | Mgi Jnum | J:203564 |
| Mgi Id | MGI:5527477 | Doi | 10.1096/fj.13-229666 |
| Citation | Takeda S, et al. (2013) Brain interstitial oligomeric amyloid beta increases with age and is resistant to clearance from brain in a mouse model of Alzheimer's disease. FASEB J 27(8):3239-48 |
| abstractText | There is a growing body of evidence that soluble oligomeric forms of amyloid beta (Abeta) play a critical role in Alzheimer's disease (AD). Despite the importance of soluble Abeta oligomers as a therapeutic target for AD, the dynamic metabolism of these Abeta species in vivo has not been elucidated because of the difficulty in monitoring brain Abeta oligomers in living animals. Here, using a unique large pore-sized membrane microdialysis, we characterized soluble Abeta oligomers in brain interstitial fluid (ISF) of awake, freely moving APP/PS1 transgenic and control WT mice. We could detect high-molecular-weight (HMW) and low-molecular-weight (LMW) Abeta oligomers in the brain ISF of living animals, which increased dramatically in an age-dependent manner (5- to 8-fold increase, 4 vs. 17-18 mo). Notably, HMW Abeta decreased more slowly than other forms of Abeta after acute gamma-secretase inhibition [% decrease from the baseline (HMW vs. LMW) was 36.9 vs. 74.1% (Abeta40, P<0.05) and 25.4 vs. 88.0% (Abeta42, P<0.01)], suggesting that HMW Abeta oligomers clear more slowly than other forms from the brain. These data reveal the dynamic metabolism of neurotoxic Abeta oligomers in AD brain and could provide new insights into Abeta-targeted therapies for AD. |
