| First Author | Yuede CM | Year | 2016 |
| Journal | J Exp Med | Volume | 213 |
| Issue | 5 | Pages | 677-85 |
| PubMed ID | 27069115 | Mgi Jnum | J:233316 |
| Mgi Id | MGI:5781252 | Doi | 10.1084/jem.20151428 |
| Citation | Yuede CM, et al. (2016) Rapid in vivo measurement of beta-amyloid reveals biphasic clearance kinetics in an Alzheimer's mouse model. J Exp Med 213(5):677-85 |
| abstractText | Findings from genetic, animal model, and human studies support the observation that accumulation of the beta-amyloid (Abeta) peptide in the brain plays a central role in the pathogenic cascade of Alzheimer's disease (AD). Human studies suggest that one key factor leading to accumulation is a defect in brain Abeta clearance. We have developed a novel microimmunoelectrode (MIE) to study the kinetics of Abeta clearance using an electrochemical approach. This is the first study using MIEs in vivo to measure rapid changes in Abeta levels in the brains of living mice. Extracellular, interstitial fluid (ISF) Abeta levels were measured in the hippocampus of APP/PS1 mice. Baseline levels of Abeta40 in the ISF are relatively stable and begin to decline within minutes of blocking Abeta production with a gamma-secretase inhibitor. Pretreatment with a P-glycoprotein inhibitor, which blocks blood-brain barrier transport of Abeta, resulted in significant prolongation of Abeta40 half-life, but only in the latter phase of Abeta clearance from the ISF. |
