{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:51:27Z","timestamp":1787017887806,"version":"build-2736575974"},"reference-count":102,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurodegener Dis"],"published-print":{"date-parts":[[2006]]},"abstract":"<jats:p>The amyloid precursor protein (APP) is a widely expressed transmembrane protein that is cleaved to generate A\u03b2 peptides in the central nervous system and is a key player in the pathogenesis of Alzheimer\u2019s disease. The precise biological functions of APP still remain unclear although various roles have been proposed. While a commonly accepted model argues that A\u03b2 peptides are the cause of onset and early pathogenesis of Alzheimer\u2019s disease, recent discussions challenge this \u2018A\u03b2 hypothesis\u2019 and suggest a direct role for APP in this neurodegenerative disease. Loss-of-function studies are an efficient way to elucidate the role of proteins and concurrently a variety of in vitro and in vivo studies has been performed for APP where protein levels have been downregulated and functional consequences monitored. Complete disruption of &lt;i&gt;APP&lt;\/i&gt; gene expression has been achieved by the generation of APP knockout animal models. Further knockdown studies using antisense and RNA interference have allowed scientists to reduce APP expression levels and have opened new avenues to explore the physiological roles of APP. In the present review, we focus on knockout and knockdown approaches that have provided insights into the physiological functions of APP and discuss their advantages and drawbacks.<\/jats:p>","DOI":"10.1159\/000094772","type":"journal-article","created":{"date-parts":[[2006,9,6]],"date-time":"2006-09-06T09:09:10Z","timestamp":1157533750000},"page":"134-147","source":"Crossref","is-referenced-by-count":36,"title":["Unraveling in vivo Functions of Amyloid Precursor Protein: Insights from Knockout and Knockdown Studies"],"prefix":"10.1159","volume":"3","author":[{"given":"Yann","family":"Senechal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Larmet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumlesh K.","family":"Dev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2006,9,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.cell.2005.02.008"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.emboj.7600061"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1002%2Fjnr.10737"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016%2FS0166-2236%2802%2902037-4"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1097%2F00019052-200404000-00003"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.expneurol.2004.11.017"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038%2Fng1718"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1097%2F00005072-199409000-00002"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016%2FS0006-8993%2800%2902869-9"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1196%2Fannals.1297.001"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.2174%2F156720506775697098"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016%2FS0197-4580%2898%2900040-2"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1002%2Fana.410270502"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1002%2Fana.410300410"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1002%2Fjnr.20408"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.emboj.7600860"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.89.22.10758"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038%2Fng0993-95"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1021%2Fbi00068a002"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.mp.4000552"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016%2FS0197-0186%2899%2900125-4"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.M311601200"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.86.7.2478"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.90.24.12045"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016%2F0006-291X%2892%2990254-I"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1016%2F0006-291X%2889%2992760-5"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1016%2F0306-4522%2893%2990304-X"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.87.4.1561"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1471-4159.1992.tb08443.x"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1006%2Fdbio.1994.1055"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1006%2Fnbdi.2000.0306"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.expneurol.2003.10.011"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1385%2FNMM%3A6%3A1%3A013"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1016%2F0896-6273%2892%2990024-8"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1016%2F0092-8674%2895%2990073-X"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1016%2F0092-8674%2894%2990066-3"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1016%2FS0166-4328%2897%2900211-8"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1749-6632.1996.tb34456.x"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.96.8.4656"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1601-183X.2004.00105.x"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.emboj.7600413"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1002%2Fjnr.20625"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1016%2FS0197-4580%2897%2900151-6"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.emboj.7600390"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1523%2FJNEUROSCI.4660-04.2005"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.emboj.7600956"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1038%2Fnrn1113"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.emboj.7600926"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.1034%2Fj.1601-183X.2002.10405.x"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1016%2FS0306-4522%2898%2900410-2"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1016%2FS0306-4522%2898%2900645-9"},{"key":"ref52","doi-asserted-by":"publisher","DOI":"10.1016%2FS0028-3908%2898%2900204-4"},{"key":"ref53","doi-asserted-by":"publisher","DOI":"10.1016%2FS0304-3940%2800%2901204-0"},{"key":"ref54","doi-asserted-by":"publisher","DOI":"10.1097%2F00001756-199809140-00025"},{"key":"ref55","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.neulet.2005.04.040"},{"key":"ref56","doi-asserted-by":"publisher","DOI":"10.1016%2FS0896-6273%2801%2900496-2"},{"key":"ref57","doi-asserted-by":"publisher","DOI":"10.1038%2F414643a"},{"key":"ref58","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.1074069"},{"key":"ref59","doi-asserted-by":"publisher","DOI":"10.1038%2Fnn0805-977"},{"key":"ref60","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.1105681"},{"key":"ref61","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.emboj.7600757"},{"key":"ref62","doi-asserted-by":"publisher","DOI":"10.1016%2F0896-6273%2889%2990252-3"},{"key":"ref63","doi-asserted-by":"publisher","DOI":"10.1016%2F0140-6736%2891%2992724-G"},{"key":"ref64","doi-asserted-by":"publisher","DOI":"10.1016%2F0304-3940%2893%2990398-5"},{"key":"ref65","doi-asserted-by":"publisher","DOI":"10.1016%2FS0006-8993%2897%2901187-6"},{"key":"ref66","doi-asserted-by":"publisher","DOI":"10.1523%2FJNEUROSCI.3291-05.2006"},{"key":"ref67","doi-asserted-by":"publisher","DOI":"10.1177%2F107385840100700507"},{"key":"ref68","doi-asserted-by":"publisher","DOI":"10.1016%2FS0079-6123%2802%2937027-4"},{"key":"ref69","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.271.5254.1406"},{"key":"ref70","doi-asserted-by":"publisher","DOI":"10.1016%2FS0006-8993%2899%2901861-2"},{"key":"ref71","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1471-4159.2004.02731.x"},{"key":"ref72","doi-asserted-by":"publisher","DOI":"10.1080%2F15216540500264620"},{"key":"ref73","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.mam.2005.07.011"},{"key":"ref74","doi-asserted-by":"publisher","DOI":"10.1038%2Fnbt915"},{"key":"ref75","doi-asserted-by":"publisher","DOI":"10.2174%2F1389450053344920"},{"key":"ref76","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1432-1033.2003.03555.x"},{"key":"ref77","doi-asserted-by":"publisher","DOI":"10.1002%2Fjnr.490310407"},{"key":"ref78","doi-asserted-by":"publisher","DOI":"10.1016%2FS0006-8993%2897%2900757-9"},{"key":"ref79","doi-asserted-by":"publisher","DOI":"10.1083%2Fjcb.128.5.919"},{"key":"ref80","doi-asserted-by":"publisher","DOI":"10.1007%2FBF02088829"},{"key":"ref81","doi-asserted-by":"publisher","DOI":"10.1242%2Fdev.01103"},{"key":"ref82","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.tins.2004.11.005"},{"key":"ref83","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1460-9568.2000.01344.x"},{"key":"ref84","doi-asserted-by":"publisher","DOI":"10.1083%2Fjcb.121.4.879"},{"key":"ref85","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.91.16.7450"},{"key":"ref86","doi-asserted-by":"publisher","DOI":"10.1016%2F0304-3940%2890%2990524-D"},{"key":"ref87","doi-asserted-by":"publisher","DOI":"10.1016%2F0006-8993%2893%2991261-P"},{"key":"ref88","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1749-6632.1996.tb34435.x"},{"key":"ref89","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.nbd.2004.11.010"},{"key":"ref90","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.neuroscience.2004.03.008"},{"key":"ref91","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.pharmthera.2005.08.006"},{"key":"ref92","doi-asserted-by":"publisher","DOI":"10.1038%2F35888"},{"key":"ref93","doi-asserted-by":"publisher","DOI":"10.1038%2Fnrm1129"},{"key":"ref94","doi-asserted-by":"publisher","DOI":"10.1038%2Fnature02873"},{"key":"ref95","doi-asserted-by":"publisher","DOI":"10.1016%2FS0304-3940%2802%2901219-3"},{"key":"ref96","doi-asserted-by":"publisher","DOI":"10.1385%2FJMN%3A24%3A1%3A123"},{"key":"ref97","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.tibtech.2004.06.004"},{"key":"ref98","doi-asserted-by":"publisher","DOI":"10.1038%2F35093537"},{"key":"ref99","doi-asserted-by":"publisher","DOI":"10.1016%2FS0006-3223%2803%2900467-0"},{"key":"ref100","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.0406214101"},{"key":"ref101","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.mp.4001687"},{"key":"ref102","doi-asserted-by":"publisher","DOI":"10.1038%2Fnm964"}],"container-title":["Neurodegenerative Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/94772","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/94772","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T22:35:15Z","timestamp":1745447715000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000094772"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006]]},"references-count":102,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2006,9,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000094772","archive":["Portico"],"relation":{},"ISSN":["1660-2854","1660-2862"],"issn-type":[{"value":"1660-2854","type":"print"},{"value":"1660-2862","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006]]}}}