{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:04:12Z","timestamp":1791270252816,"version":"4.1.0"},"reference-count":62,"publisher":"Society for Neuroscience","issue":"1","license":[{"start":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T00:00:00Z","timestamp":1372723200000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2013,1,2]]},"abstract":"<jats:p>Apolipoprotein E (APOE) is the major risk factor for sporadic Alzheimer's disease. Among other functions, APOE is proposed to sequester neurotoxic amyloid-\u03b2 (A\u03b2) peptides in the brain, delivering them to cellular catabolism via neuronal APOE receptors. Still, the receptors involved in this process remain controversial. Here, we identified the pro-neurotrophin receptor sortilin as major endocytic pathway for clearance of APOE\/A\u03b2 complexes in neurons. Sortilin binds APOE with high affinity. Lack of receptor expression in mice results in accumulation of APOE and of A\u03b2 in the brain and in aggravated plaque burden. Also, primary neurons lacking sortilin exhibit significantly impaired uptake of APOE\/A\u03b2 complexes despite proper expression of other APOE receptors. Despite higher than normal brain APOE levels, sortilin-deficient animals display anomalies in brain lipid metabolism (e.g., accumulation of sulfatides) seen in APOE-deficient mice, indicating functional deficiency in cellular APOE uptake pathways. Together, our findings identified sortilin as an essential neuronal pathway for APOE-containing lipoproteins<jats:italic>in vivo<\/jats:italic>and suggest an intriguing link between A\u03b2 catabolism and pro-neurotrophin signaling converging on this receptor.<\/jats:p>","DOI":"10.1523\/jneurosci.2425-12.2013","type":"journal-article","created":{"date-parts":[[2013,1,2]],"date-time":"2013-01-02T19:23:01Z","timestamp":1357154581000},"page":"358-370","source":"Crossref","is-referenced-by-count":109,"title":["The Pro-Neurotrophin Receptor Sortilin Is a Major Neuronal Apolipoprotein E Receptor for Catabolism of Amyloid-\u03b2 Peptide in the Brain"],"prefix":"10.1523","volume":"33","author":[{"given":"Anne-Sophie","family":"Carlo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Gustafsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Mastrobuoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten S.","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman","family":"Burgert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Hartl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Rohe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Nykjaer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Herz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Heeren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kempa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus Munck","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Willnow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2013,1,2]]},"reference":[{"key":"2023041304004668000_33.1.358.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503689102"},{"key":"2023041304004668000_33.1.358.2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-263"},{"key":"2023041304004668000_33.1.358.3","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002156"},{"key":"2023041304004668000_33.1.358.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1206446109"},{"key":"2023041304004668000_33.1.358.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914984107"},{"key":"2023041304004668000_33.1.358.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.07.020"},{"key":"2023041304004668000_33.1.358.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"2023041304004668000_33.1.358.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.1217697"},{"key":"2023041304004668000_33.1.358.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.07.017"},{"key":"2023041304004668000_33.1.358.10","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2001.1016"},{"key":"2023041304004668000_33.1.358.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0230450100"},{"key":"2023041304004668000_33.1.358.12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.170217"},{"key":"2023041304004668000_33.1.358.13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502143200"},{"key":"2023041304004668000_33.1.358.14","doi-asserted-by":"publisher","DOI":"10.1038\/373523a0"},{"key":"2023041304004668000_33.1.358.15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212340200"},{"key":"2023041304004668000_33.1.358.16","doi-asserted-by":"crossref","first-page":"3862","DOI":"10.1074\/jbc.M309475200","article-title":"Astroglial regulation of apolipoprotein E expression in neuronal cells. 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