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Induced degeneration of the locus ceruleus increased expression of inflammatory mediators in APP-transgenic mice and resulted in elevated A\u03b2 deposition. In vivo laser microscopy confirmed a reduced recruitment of microglia to A\u03b2 plaque sites and impaired microglial A\u03b2 phagocytosis in NE-depleted APP-transgenic mice. Supplying the mice the norepinephrine precursor L-threo-DOPS restored microglial functions in NE-depleted mice. This indicates that decrease of NE in locus ceruleus projection areas facilitates the inflammatory reaction of microglial cells in AD and impairs microglial migration and phagocytosis, thereby contributing to reduced A\u03b2 clearance. Consequently, therapies targeting microglial phagocytosis should be tested under NE depletion.<\/jats:p>","DOI":"10.1073\/pnas.0909586107","type":"journal-article","created":{"date-parts":[[2010,3,15]],"date-time":"2010-03-15T23:59:34Z","timestamp":1268697574000},"page":"6058-6063","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":474,"title":["Locus ceruleus controls Alzheimer's disease pathology by modulating microglial functions through norepinephrine"],"prefix":"10.1073","volume":"107","author":[{"given":"Michael T.","family":"Heneka","sequence":"first","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen and Department of Neurology, University of Bonn, 53105 Bonn, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Nadrigny","sequence":"additional","affiliation":[{"name":"Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 G\u00f6ttingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommy","family":"Regen","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University of G\u00f6ttingen, 37075 G\u00f6ttingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Martinez-Hernandez","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Biophysical Chemistry, Am Fassberg 11, 37077 G\u00f6ttingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Dumitrescu-Ozimek","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen and Department of Neurology, University of Bonn, 53105 Bonn, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dick","family":"Terwel","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen and Department of Neurology, University of Bonn, 53105 Bonn, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Jardanhazi-Kurutz","sequence":"additional","affiliation":[{"name":"Bayer Schering Pharma, 13353 Berlin, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Walter","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen and Department of Neurology, University of Bonn, 53105 Bonn, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Kirchhoff","sequence":"additional","affiliation":[{"name":"Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 G\u00f6ttingen, Germany;"},{"name":"Molecular Physiology, Institute of Physiology, University of Saarland, 66421 Homburg\/Saar, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe-Karsten","family":"Hanisch","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University of G\u00f6ttingen, 37075 G\u00f6ttingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus P.","family":"Kummer","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen and Department of Neurology, University of Bonn, 53105 Bonn, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,3,15]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"266","article-title":"Pathology of Parkinsonism: A preliminary report of 24 cases","author":"Forno L","year":"1966","unstructured":"L Forno, Pathology of Parkinsonism: A preliminary report of 24 cases. 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