{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T20:29:02Z","timestamp":1789072142436,"version":"build-2803163510"},"reference-count":37,"publisher":"Society for Neuroscience","issue":"39","license":[{"start":{"date-parts":[[2012,3,28]],"date-time":"2012-03-28T00:00:00Z","timestamp":1332892800000},"content-version":"vor","delay-in-days":182,"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":[[2011,9,28]]},"abstract":"<jats:p>Amyloid precursor protein (APP) has long been linked to the neurodegeneration of Alzheimer's disease (AD), but the associated cell death has been difficult to capture<jats:italic>in vivo<\/jats:italic>, and the role of APP in effecting neuron loss is still unclear. Olfactory dysfunction is an early symptom of AD with amyloid pathology in the olfactory epithelium correlating well to the brain pathology of AD patients. As olfactory sensory neurons (OSNs) regenerate continuously with immature and mature OSNs coexisting in the same olfactory epithelium, we sought to use this unique system to study APP-induced neurodegeneration. Here we have developed an olfactory-based transgenic mouse model that overexpresses humanized APP containing familial AD mutations (hAPP) in either mature or immature OSNs, and found that despite the absence of extracellular plaques a striking number of apoptotic neurons were detected by 3 weeks of age. Importantly, apoptosis was restricted to the specific population overexpressing hAPP, either mature or immature OSNs, sparing those without hAPP. Interestingly, we observed that this widespread neurodegeneration could be rapidly rescued by reducing hAPP expression levels in immature neurons. Together, these data argue that overexpressing hAPP alone could induce cell-autonomous apoptosis in both mature and immature neurons, challenging the notion that amyloid plaques are necessary for neurodegeneration. Furthermore, we show that hAPP-induced neurodegeneration is reversible, suggesting that AD-related neural loss could potentially be rescued. Thus, we propose that this unique<jats:italic>in vivo<\/jats:italic>model will not only help determine the mechanisms underlying AD-related neurodegeneration but also serve as a platform to test possible treatments.<\/jats:p>","DOI":"10.1523\/jneurosci.1714-11.2011","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T20:25:18Z","timestamp":1317241518000},"page":"13699-13704","source":"Crossref","is-referenced-by-count":33,"title":["<i>In Vivo<\/i>Olfactory Model of APP-Induced Neurodegeneration Reveals a Reversible Cell-Autonomous Function"],"prefix":"10.1523","volume":"31","author":[{"given":"Ning","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaibin","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Belluscio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2011,9,28]]},"reference":[{"key":"2023041303524370000_31.39.13699.1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21910"},{"key":"2023041303524370000_31.39.13699.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1998.tb10651.x"},{"key":"2023041303524370000_31.39.13699.3","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2010.00008"},{"key":"2023041303524370000_31.39.13699.4","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(199605)30:1<67::AID-NEU7>3.0.CO;2-E"},{"key":"2023041303524370000_31.39.13699.5","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1993.1201"},{"key":"2023041303524370000_31.39.13699.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0707-05.2005"},{"key":"2023041303524370000_31.39.13699.7","doi-asserted-by":"publisher","DOI":"10.1177\/1073858408315026"},{"key":"2023041303524370000_31.39.13699.8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1717-10.2010"},{"key":"2023041303524370000_31.39.13699.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012974"},{"key":"2023041303524370000_31.39.13699.10","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0312-8"},{"key":"2023041303524370000_31.39.13699.11","doi-asserted-by":"publisher","DOI":"10.1002\/msj.20159"},{"key":"2023041303524370000_31.39.13699.12","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(90)90017-5"},{"key":"2023041303524370000_31.39.13699.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.12.5547"},{"key":"2023041303524370000_31.39.13699.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.05.022"},{"key":"2023041303524370000_31.39.13699.15","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"2023041303524370000_31.39.13699.16","doi-asserted-by":"publisher","DOI":"10.1002\/mds.10379"},{"key":"2023041303524370000_31.39.13699.17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020355"},{"key":"2023041303524370000_31.39.13699.18","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2168"},{"key":"2023041303524370000_31.39.13699.19","doi-asserted-by":"publisher","DOI":"10.1038\/35093537"},{"key":"2023041303524370000_31.39.13699.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2010.02.003"},{"key":"2023041303524370000_31.39.13699.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.10.050"},{"key":"2023041303524370000_31.39.13699.22","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00434-3"},{"key":"2023041303524370000_31.39.13699.23","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.25.2.209"},{"key":"2023041303524370000_31.39.13699.24","doi-asserted-by":"crossref","first-page":"3896","DOI":"10.1523\/JNEUROSCI.12-10-03896.1992","article-title":"Olfactory sensory neurons are trophically dependent on the olfactory bulb for their prolonged survival","volume":"12","author":"Schwob","year":"1992","journal-title":"J Neurosci"},{"key":"2023041303524370000_31.39.13699.25","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199412000-00031"},{"key":"2023041303524370000_31.39.13699.26","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-010-0242-4"},{"key":"2023041303524370000_31.39.13699.27","doi-asserted-by":"publisher","DOI":"10.1038\/337736a0"},{"key":"2023041303524370000_31.39.13699.28","first-page":"13","article-title":"Synapses, synaptic activity and intraneuronal abeta in Alzheimer's disease","volume":"2","author":"Tampellini","year":"2010","journal-title":"Front Aging Neurosci"},{"key":"2023041303524370000_31.39.13699.29","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s11068-007-9012-5","article-title":"Changes in the distribution of calcium calmodulin-dependent protein kinase II at the presynaptic bouton after depolarization","volume":"35","author":"Tao-Cheng","year":"2006","journal-title":"Brain Cell Biol"},{"key":"2023041303524370000_31.39.13699.30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R800019200"},{"key":"2023041303524370000_31.39.13699.31","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1097\/00005072-199611000-00004","article-title":"In situ labeling of dying cortical neurons in normal aging and in Alzheimer's disease: correlations with senile plaques and disease progression","volume":"55","author":"Troncoso","year":"1996","journal-title":"J Neuropathol Exp Neurol"},{"key":"2023041303524370000_31.39.13699.32","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21973"},{"key":"2023041303524370000_31.39.13699.33","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1523\/JNEUROSCI.09-02-00683.1989","article-title":"The expression of the growth associated protein B50\/GAP43 in the olfactory system of neonatal and adult rats","volume":"9","author":"Verhaagen","year":"1989","journal-title":"J Neurosci"},{"key":"2023041303524370000_31.39.13699.34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4622-09.2010"},{"key":"2023041303524370000_31.39.13699.35","first-page":"723782","article-title":"Neuron loss in transgenic mouse models of Alzheimer's disease","volume":"2010","author":"Wirths","year":"2010","journal-title":"Int J Alzheimers Dis"},{"key":"2023041303524370000_31.39.13699.36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02737.x"},{"key":"2023041303524370000_31.39.13699.37","doi-asserted-by":"publisher","DOI":"10.1038\/35037739"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.1714-11.2011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T20:40:20Z","timestamp":1681418420000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.1714-11.2011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9,28]]},"references-count":37,"journal-issue":{"issue":"39","published-online":{"date-parts":[[2011,9,28]]},"published-print":{"date-parts":[[2011,9,28]]}},"alternative-id":["10.1523\/JNEUROSCI.1714-11.2011"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.1714-11.2011","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,9,28]]}}}