{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T11:48:52Z","timestamp":1771501732698,"version":"3.50.1"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,30]],"date-time":"2017-08-30T00:00:00Z","timestamp":1504051200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,30]],"date-time":"2017-08-30T00:00:00Z","timestamp":1504051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzheimer\u2019s disease is a major neurodegenerative disorder that leads to severe cognitive deficits in the elderly population. Over the past two decades, multiple studies have focused on elucidating the causative factors underlying memory defects in Alzheimer\u2019s patients. In this regard, new evidence linking Alzheimer\u2019s disease-related pathology and neuronal stem cells suggests that hippocampal neurogenesis impairment is an important factor underlying these cognitive deficits. However, because of conflicting results, the impact of A\u03b2 pathology on neurogenesis\/gliogenesis remains unclear. Here, we investigated the effect of A\u03b2 on neuronal and glial proliferation by using an APP\/PS1 transgenic model and <jats:italic>in vitro<\/jats:italic> assays. Specifically, we showed that neurogenesis is affected early in the APP\/PS1 hippocampus, as evidenced by a significant decrease in the proliferative activity due to a reduced number of both radial glia-like neural stem cells (type-1 cells) and intermediate progenitor cells (type-2 cells). Moreover, we demonstrated that soluble A\u03b2 from APP\/PS1 mice impairs neuronal cell proliferation using neurosphere cultures. On the other hand, we showed that oligomeric A\u03b2 stimulates microglial proliferation, whereas no effect was observed on astrocytes. These findings indicate that A\u03b2 has a differential effect on hippocampal proliferative cells by inhibiting neuronal proliferation and triggering the formation of microglial cells.<\/jats:p>","DOI":"10.1038\/s41598-017-10353-7","type":"journal-article","created":{"date-parts":[[2017,8,24]],"date-time":"2017-08-24T15:38:19Z","timestamp":1503589099000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Dual roles of A\u03b2 in proliferative processes in an amyloidogenic model of Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"7","author":[{"given":"David","family":"Baglietto-Vargas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"S\u00e1nchez-Mejias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebasti\u00e1n","family":"Jimenez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Trujillo-Estrada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"G\u00f3mez-Arboledas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"S\u00e1nchez-Mico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"S\u00e1nchez-Varo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marisa","family":"Vizuete","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Carlos","family":"D\u00e1vila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Manuel","family":"Garc\u00eda-Verdugo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Vitorica","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Gutierrez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,8,30]]},"reference":[{"key":"10353_CR1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002369","volume":"3","author":"DM Holtzman","year":"2011","unstructured":"Holtzman, D. M., Morris, J. C. & Goate, A. M. Alzheimer\u2019s disease: the challenge of the second century. Sci Transl Med \n                           3, 77sr71, doi:10.1126\/scitranslmed.3002369 (2011).","journal-title":"Sci Transl Med"},{"key":"10353_CR2","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1056\/NEJMra0909142","volume":"362","author":"HW Querfurth","year":"2010","unstructured":"Querfurth, H. W. & LaFerla, F. M. Alzheimer\u2019s disease. N Engl J Med \n                           362, 329\u2013344, doi:10.1056\/NEJMra0909142 (2010).","journal-title":"N Engl J Med"},{"key":"10353_CR3","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021287","volume":"7","author":"B Winner","year":"2015","unstructured":"Winner, B. & Winkler, J. Adult neurogenesis in neurodegenerative diseases. Cold Spring Harb Perspect Biol \n                           7, a021287, doi:10.1101\/cshperspect.a021287 (2015).","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"10353_CR4","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.pneurobio.2013.12.006","volume":"115","author":"L Ruan","year":"2014","unstructured":"Ruan, L. et al. Neurogenesis in neurological and psychiatric diseases and brain injury: from bench to bedside. Prog Neurobiol \n                           115, 116\u2013137, doi:10.1016\/j.pneurobio.2013.12.006 (2014).","journal-title":"Prog Neurobiol"},{"key":"10353_CR5","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.nlm.2013.07.011","volume":"105","author":"YW Pan","year":"2013","unstructured":"Pan, Y. W., Storm, D. R. & Xia, Z. Role of adult neurogenesis in hippocampus-dependent memory, contextual fear extinction and remote contextual memory: new insights from ERK5 MAP kinase. Neurobiol Learn Mem \n                           105, 81\u201392, doi:10.1016\/j.nlm.2013.07.011 (2013).","journal-title":"Neurobiol Learn Mem"},{"key":"10353_CR6","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-6-85","volume":"6","author":"Y Mu","year":"2011","unstructured":"Mu, Y. & Gage, F. H. Adult hippocampal neurogenesis and its role in Alzheimer\u2019s disease. Molecular neurodegeneration \n                           6, 85, doi:10.1186\/1750-1326-6-85 (2011).","journal-title":"Molecular neurodegeneration"},{"key":"10353_CR7","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/nature09817","volume":"472","author":"A Sahay","year":"2011","unstructured":"Sahay, A. et al. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature \n                           472, 466\u2013470, doi:10.1038\/nature09817 (2011).","journal-title":"Nature"},{"key":"10353_CR8","doi-asserted-by":"publisher","first-page":"3359","DOI":"10.1093\/brain\/awq215","volume":"133","author":"R Coras","year":"2010","unstructured":"Coras, R. et al. Low proliferation and differentiation capacities of adult hippocampal stem cells correlate with memory dysfunction in humans. Brain \n                           133, 3359\u20133372, doi:10.1093\/brain\/awq215 (2010).","journal-title":"Brain"},{"key":"10353_CR9","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/nrn2822","volume":"11","author":"W Deng","year":"2010","unstructured":"Deng, W., Aimone, J. B. & Gage, F. H. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nature reviews. Neuroscience \n                           11, 339\u2013350, doi:10.1038\/nrn2822 (2010).","journal-title":"Nature reviews. 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Young hippocampal neurons are critical for recent and remote spatial memory in adult mice. Neuroscience \n                           171, 769\u2013778, doi:10.1016\/j.neuroscience.2010.09.047 (2010).","journal-title":"Neuroscience"},{"key":"10353_CR13","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/35066584","volume":"410","author":"TJ Shors","year":"2001","unstructured":"Shors, T. J. et al. Neurogenesis in the adult is involved in the formation of trace memories. Nature \n                           410, 372\u2013376, doi:10.1038\/35066584 (2001).","journal-title":"Nature"},{"key":"10353_CR14","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/6368","volume":"2","author":"H van Praag","year":"1999","unstructured":"van Praag, H., Kempermann, G. & Gage, F. H. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. 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Neurobiology of disease \n                           47, 155\u2013162, doi:10.1016\/j.nbd.2012.03.033 (2012).","journal-title":"Neurobiology of disease"},{"key":"10353_CR17","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1073\/pnas.2634794100","volume":"101","author":"K Jin","year":"2004","unstructured":"Jin, K. et al. Increased hippocampal neurogenesis in Alzheimer\u2019s disease. Proceedings of the National Academy of Sciences of the United States of America \n                           101, 343\u2013347, doi:10.1073\/pnas.2634794100 (2004).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10353_CR18","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/693851","volume":"2014","author":"MW Marlatt","year":"2014","unstructured":"Marlatt, M. W. et al. Proliferation in the Alzheimer hippocampus is due to microglia, not astroglia, and occurs at sites of amyloid deposition. 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The Journal of neuroscience: the official journal of the Society for Neuroscience \n                           30, 12252\u201312262, doi:10.1523\/JNEUROSCI.1305-10.2010 (2010).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"10353_CR21","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1097\/nen.0b013e318160c5db","volume":"67","author":"B Li","year":"2008","unstructured":"Li, B. et al. Failure of neuronal maturation in Alzheimer disease dentate gyrus. Journal of neuropathology and experimental neurology \n                           67, 78\u201384, doi:10.1097\/nen.0b013e318160c5db (2008).","journal-title":"Journal of neuropathology and experimental neurology"},{"key":"10353_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nbd.2006.04.017","volume":"24","author":"K Boekhoorn","year":"2006","unstructured":"Boekhoorn, K., Joels, M. & Lucassen, P. J. Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus. Neurobiology of disease \n                           24, 1\u201314, doi:10.1016\/j.nbd.2006.04.017 (2006).","journal-title":"Neurobiology of disease"},{"key":"10353_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076497","volume":"8","author":"A Krezymon","year":"2013","unstructured":"Krezymon, A. et al. Modifications of hippocampal circuits and early disruption of adult neurogenesis in the tg2576 mouse model of Alzheimer\u2019s disease. PloS one \n                           8, e76497, doi:10.1371\/journal.pone.0076497 (2013).","journal-title":"PloS one"},{"key":"10353_CR24","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1002\/jnr.22387","volume":"88","author":"M Demars","year":"2010","unstructured":"Demars, M., Hu, Y. S., Gadadhar, A. & Lazarov, O. Impaired neurogenesis is an early event in the etiology of familial Alzheimer\u2019s disease in transgenic mice. J Neurosci Res \n                           88, 2103\u20132117, doi:10.1002\/jnr.22387 (2010).","journal-title":"J Neurosci Res"},{"key":"10353_CR25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002935","volume":"3","author":"JJ Rodriguez","year":"2008","unstructured":"Rodriguez, J. J. et al. Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer\u2019s disease. PloS one \n                           3, e2935, doi:10.1371\/journal.pone.0002935 (2008).","journal-title":"PloS one"},{"key":"10353_CR26","doi-asserted-by":"publisher","first-page":"6771","DOI":"10.1523\/JNEUROSCI.5564-06.2007","volume":"27","author":"L Verret","year":"2007","unstructured":"Verret, L., Jankowsky, J. L., Xu, G. M., Borchelt, D. R. & Rampon, C. Alzheimer\u2019s-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis. The Journal of neuroscience: the official journal of the Society for Neuroscience \n                           27, 6771\u20136780, doi:10.1523\/JNEUROSCI.5564-06.2007 (2007).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"10353_CR27","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/7854_2012_237","volume":"15","author":"MW Marlatt","year":"2013","unstructured":"Marlatt, M. W., Potter, M. C., Bayer, T. A., van Praag, H. & Lucassen, P. J. Prolonged running, not fluoxetine treatment, increases neurogenesis, but does not alter neuropathology, in the 3xTg mouse model of Alzheimer\u2019s disease. Curr Top Behav Neurosci \n                           15, 313\u2013340, doi:10.1007\/7854_2012_237 (2013).","journal-title":"Curr Top Behav Neurosci"},{"key":"10353_CR28","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1002\/hipo.20587","volume":"19","author":"Y Yu","year":"2009","unstructured":"Yu, Y. et al. Increased hippocampal neurogenesis in the progressive stage of Alzheimer\u2019s disease phenotype in an APP\/PS1 double transgenic mouse model. Hippocampus \n                           19, 1247\u20131253, doi:10.1002\/hipo.20587 (2009).","journal-title":"Hippocampus"},{"key":"10353_CR29","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s00401-008-0380-4","volume":"116","author":"R Kolecki","year":"2008","unstructured":"Kolecki, R. et al. The effect of amyloidosis-beta and ageing on proliferation of neuronal progenitor cells in APP-transgenic mouse hippocampus and in culture. 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