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Human studies suggest that one key factor leading to accumulation is a defect in brain A\u03b2 clearance. We have developed a novel microimmunoelectrode (MIE) to study the kinetics of A\u03b2 clearance using an electrochemical approach. This is the first study using MIEs in vivo to measure rapid changes in A\u03b2 levels in the brains of living mice. Extracellular, interstitial fluid (ISF) A\u03b2 levels were measured in the hippocampus of APP\/PS1 mice. Baseline levels of A\u03b240 in the ISF are relatively stable and begin to decline within minutes of blocking A\u03b2 production with a \u03b3-secretase inhibitor. Pretreatment with a P-glycoprotein inhibitor, which blocks blood\u2013brain barrier transport of A\u03b2, resulted in significant prolongation of A\u03b240 half-life, but only in the latter phase of A\u03b2 clearance from the ISF.<\/jats:p>","DOI":"10.1084\/jem.20151428","type":"journal-article","created":{"date-parts":[[2016,4,11]],"date-time":"2016-04-11T14:12:28Z","timestamp":1460383948000},"page":"677-685","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":59,"title":["Rapid in vivo measurement of \u03b2-amyloid reveals biphasic clearance kinetics in an Alzheimer\u2019s mouse model"],"prefix":"10.1084","volume":"213","author":[{"given":"Carla M.","family":"Yuede","sequence":"first","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Restivo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd A.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane C.","family":"Hettinger","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare E.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret R.","family":"Hayne","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojun","family":"Bu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-zhong","family":"Li","sequence":"additional","affiliation":[{"name":"Nanobioengineering\/Bioelectronics Laboratory, Department of Biomedical Engineering, Florida International University, Miami, FL 33199 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Cirrito","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2016,4,11]]},"reference":[{"key":"2023072603263384400_bib1","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.2967\/jnumed.108.051235","article-title":"Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET","volume":"49","author":"Bankstahl","year":"2008","journal-title":"J. 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