{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T20:49:56Z","timestamp":1773175796353,"version":"3.50.1"},"reference-count":24,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5927","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2009,5]]},"abstract":"<jats:title>Tactical Target<\/jats:title>\n                  <jats:p>\n                    Intramembrane proteolysis by the \u03b3-secretase complex is important during development and in the pathology of Alzheimer's disease. \u03b3-Secretase has usually been considered as a homogeneous activity.\n                    <jats:bold>\n                      Serneels\n                      <jats:italic>et al.<\/jats:italic>\n                    <\/jats:bold>\n                    (p.\n                    <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" page=\"639\" related-article-type=\"in-this-issue\" vol=\"324\" xlink:href=\"10.1126\/science.1171176\">639<\/jats:related-article>\n                    , published online 19 March; see the Perspective by\n                    <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" page=\"603\" related-article-type=\"in-this-issue\" vol=\"324\" xlink:href=\"10.1126\/science.1174267\">\n                      <jats:bold>Golde and Kukar<\/jats:bold>\n                    <\/jats:related-article>\n                    ) now show that the Aph1B component of the \u03b3-secretase complex is responsible for the generation of long \u03b2-amyloid species involved in Alzheimer's disease. In a mouse model of Alzheimer's disease, full knockout of Aph1B improved disease phenotypes, without the sort of toxicity previously observed when targeting \u03b3-secretase more generally.\n                  <\/jats:p>","DOI":"10.1126\/science.1171176","type":"journal-article","created":{"date-parts":[[2009,3,19]],"date-time":"2009-03-19T21:42:38Z","timestamp":1237498958000},"page":"639-642","source":"Crossref","is-referenced-by-count":221,"title":["\u03b3-Secretase Heterogeneity in the Aph1 Subunit: Relevance for Alzheimer\u2019s Disease"],"prefix":"10.1126","volume":"324","author":[{"given":"Lutgarde","family":"Serneels","sequence":"first","affiliation":[{"name":"Department for Molecular and Developmental Genetics, VIB, KULeuven, Herestraat 49, 3000 Leuven, Belgium."},{"name":"Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium."}]},{"given":"J\u00e9r\u00f4me","family":"Van Biervliet","sequence":"additional","affiliation":[{"name":"Department for Molecular and Developmental Genetics, VIB, KULeuven, Herestraat 49, 3000 Leuven, Belgium."},{"name":"Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium."}]},{"given":"Katleen","family":"Craessaerts","sequence":"additional","affiliation":[{"name":"Department for Molecular and Developmental Genetics, VIB, KULeuven, Herestraat 49, 3000 Leuven, Belgium."},{"name":"Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium."}]},{"given":"Tim","family":"Dejaegere","sequence":"additional","affiliation":[{"name":"Department for Molecular and Developmental Genetics, VIB, KULeuven, Herestraat 49, 3000 Leuven, Belgium."},{"name":"Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium."}]},{"given":"Katrien","family":"Horr\u00e9","sequence":"additional","affiliation":[{"name":"Department for Molecular and Developmental Genetics, VIB, KULeuven, Herestraat 49, 3000 Leuven, Belgium."},{"name":"Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium."}]},{"given":"Tine","family":"Van Houtvin","sequence":"additional","affiliation":[{"name":"Department for Molecular and Developmental Genetics, VIB, KULeuven, Herestraat 49, 3000 Leuven, Belgium."},{"name":"Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium."}]},{"given":"Hermann","family":"Esselmann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, 91054 Erlangen, Germany."},{"name":"Department of Psychiatry and Psychotherapy, Rhine State Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany."}]},{"given":"Sabine","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, 91054 Erlangen, Germany."},{"name":"Department of Psychiatry and Psychotherapy, Rhine State Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany."}]},{"given":"Martin 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