{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T07:38:03Z","timestamp":1762673883286},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,6,15]],"date-time":"2012-06-15T00:00:00Z","timestamp":1339718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cumulative evidence indicates that aberrant re\u2010expression of many cell cycle\u2010related proteins and inappropriate neuronal cell cycle control are critical events in Alzheimer\u2019s disease (AD) pathogenesis. Evidence of cell cycle activation in post\u2010mitotic neurons has also been observed in murine models of AD, despite the fact that most of these mice do not show massive loss of neuronal bodies. Dysfunction of the cell cycle appears to affect cells other than neurons, as peripheral cells, such as lymphocytes and fibroblasts from patients with AD, show an altered response to mitogenic stimulation. We sought to determine whether cell cycle disturbances are present simultaneously in both brain and peripheral cells from the amyloid precursor protein (APP)\/presenilin 1 (PS1) mouse model of AD, in order to validate the use of peripheral cells from patients not only to study cell cycle abnormalities as a pathogenic feature of AD, but also as a means to test novel therapeutic approaches. By using cell cycle pathway\u2010specific RT<jats:sup>2<\/jats:sup>Profiler\u2122 PCR Arrays, we detected changes in a number of cell cycle\u2010related genes in brain as well as in lymphocytes from APP\/PS1 mice. Moreover, we found enhanced 5\u2032\u2010bromo\u20102\u2032\u2010deoxyuridine incorporation into DNA in lymphocytes from APP\/PS1 mice, and increased expression of the cell proliferation marker proliferating cell nuclear antigen (PCNA), and the cyclin\u2010dependent kinase (CDK) inhibitor Cdkn2a, as detected by immunohistochemistry in cortical neurons of the APP\/PS1 mice. Taken together, the cell cycle\u2010related changes in brain and blood cells reported here support the mitosis failure hypothesis in AD and validate the use of peripheral cells as surrogate tissue to study the molecular basis of AD pathogenesis.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2012.08178.x","type":"journal-article","created":{"date-parts":[[2012,6,15]],"date-time":"2012-06-15T15:43:10Z","timestamp":1339774990000},"page":"2609-2618","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Altered cell cycle\u2010related gene expression in brain and lymphocytes from a transgenic mouse model of Alzheimer\u2019s disease [amyloid precursor protein\/presenilin 1 (PS1)]"],"prefix":"10.1111","volume":"36","author":[{"given":"Noem\u00ed","family":"Esteras","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Bartolom\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Alqu\u00e9zar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Desire\u00e9","family":"Antequera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00darsula","family":"Mu\u00f1oz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Carro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1ngeles","family":"Mart\u00edn\u2010Requero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,6,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21690"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.06.018"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2003.09.007"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199611250-00050"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms10041609"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090955"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-7081-3"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2010.01064.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-08-02801.1998"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01663-5"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-9961(03)00040-8"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2000.0378"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)01618-4"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1667\/RR3211"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205711"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.2.470"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.200700059"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01724"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2124"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0198-097"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007280"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061781"},{"key":"e_1_2_8_24_1","doi-asserted-by":"crossref","first-page":"541","DOI":"10.3233\/JAD-2009-0993","article-title":"Activation of cell cycle proteins in transgenic mice in response to neuronal loss but not amyloid\u2010beta and tau pathology","volume":"16","author":"Lopes J.P.","year":"2009","journal-title":"J. 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