{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:10:51Z","timestamp":1789387851124,"version":"build-2803163510"},"reference-count":16,"publisher":"Society for Neuroscience","issue":"10","license":[{"start":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T00:00:00Z","timestamp":1409875200000},"content-version":"vor","delay-in-days":184,"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":[[2014,3,5]]},"abstract":"<jats:p>Rare, familial, early-onset autosomal dominant forms of familial Alzheimer's disease (FAD) are caused by mutations in genes encoding \u03b2-amyloid (A\u03b2) precursor protein (APP), presenilin-1 (PS1), and presenilin-2. Each of these genes is expressed ubiquitously throughout the CNS, but a widely held view is that excitatory neurons are the primary (or sole) source of the A\u03b2 peptides that promote synaptic dysfunction and neurodegeneration. These efforts notwithstanding, APP and the enzymes required for A\u03b2 production are synthesized by many additional cell types, and the degree to which those cells contribute to the production of A\u03b2 that drives deposition in the CNS has not been tested. We generated transgenic mice in which expression of an ubiquitously expressed, FAD-linked mutant<jats:italic>PSEN1<\/jats:italic>gene was selectively inactivated within postnatal forebrain excitatory neurons, with continued synthesis in all other cells in the CNS. When combined with an additional transgene encoding an FAD-linked APP \u201cSwedish\u201d variant that is synthesized broadly within the CNS, cerebral A\u03b2 deposition during aging was found to be unaffected relative to mice with continued mutant PS1 synthesis in excitatory neurons. Thus, A\u03b2 accumulation is non-cell autonomous, with the primary age-dependent contribution to cerebral A\u03b2 deposition arising from mutant PS1-dependent cleavage of APP within cells other than excitatory neurons.<\/jats:p>","DOI":"10.1523\/jneurosci.5079-13.2014","type":"journal-article","created":{"date-parts":[[2014,3,5]],"date-time":"2014-03-05T17:36:35Z","timestamp":1394040995000},"page":"3668-3673","source":"Crossref","is-referenced-by-count":48,"title":["Age-Dependent, Non-Cell-Autonomous Deposition of Amyloid from Synthesis of \u03b2-Amyloid by Cells Other Than Excitatory Neurons"],"prefix":"10.1523","volume":"34","author":[{"given":"Karthikeyan","family":"Veeraraghavalu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph E.","family":"Tanzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangram S.","family":"Sisodia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2014,3,5]]},"reference":[{"key":"2023041304094162000_34.10.3668.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80974-5"},{"key":"2023041304094162000_34.10.3668.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.07.033"},{"key":"2023041304094162000_34.10.3668.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.10.028"},{"key":"2023041304094162000_34.10.3668.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00205-8"},{"key":"2023041304094162000_34.10.3668.5","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(92)90202-M"},{"key":"2023041304094162000_34.10.3668.6","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(90)90100-T"},{"key":"2023041304094162000_34.10.3668.7","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.1523\/JNEUROSCI.11-12-03783.1991","article-title":"Processing of beta-amyloid precursor protein in microglia and astrocytes favors an internal localization over constitutive secretion","volume":"11","author":"Haass","year":"1991","journal-title":"J Neurosci"},{"key":"2023041304094162000_34.10.3668.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00124-7"},{"key":"2023041304094162000_34.10.3668.9","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1523\/JNEUROSCI.17-06-01971.1997","article-title":"Light and electron microscopic localization of presenilin-1 in primate brain","volume":"17","author":"Lah","year":"1997","journal-title":"J Neurosci"},{"key":"2023041304094162000_34.10.3668.10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.13.7104"},{"key":"2023041304094162000_34.10.3668.11","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.21.1.479"},{"key":"2023041304094162000_34.10.3668.12","doi-asserted-by":"publisher","DOI":"10.1038\/375754a0"},{"key":"2023041304094162000_34.10.3668.13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.45.28415"},{"key":"2023041304094162000_34.10.3668.14","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81826-7"},{"key":"2023041304094162000_34.10.3668.15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1302106110"},{"key":"2023041304094162000_34.10.3668.16","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235505"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.5079-13.2014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T22:00:17Z","timestamp":1681423217000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.5079-13.2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,5]]},"references-count":16,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,3,5]]},"published-print":{"date-parts":[[2014,3,5]]}},"alternative-id":["10.1523\/JNEUROSCI.5079-13.2014"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.5079-13.2014","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,5]]}}}