{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:29:31Z","timestamp":1791066571611,"version":"4.1.0"},"reference-count":54,"publisher":"Cold Spring Harbor Laboratory","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Learn. Mem."],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:p>The apolipoprotein E4 (<jats:italic>APOE-\u03b54<\/jats:italic>) allele is the strongest genetic risk factor for developing late-onset Alzheimer\u2019s disease, and may predispose individuals to Alzheimer\u2019s-related cognitive decline by affecting normal brain function early in life. To investigate the impact of human APOE alleles on cognitive performance in mice, we trained 3-mo-old APOE targeted replacement mice (E2, E3, and E4) in the Barnes maze to locate and enter a target hole along the perimeter of the maze. Long-term spatial memory was probed 24 h and 72 h after training. We found that young E4 mice exhibited significantly impaired spatial learning and memory in the Barnes maze compared to E3 mice. Deficits in spatial cognition were also present in a second independent cohort of E4 mice tested at 18 mo of age. In contrast, cognitive performance in the hidden platform water maze was not as strongly affected by APOE genotype. We also examined the dendritic morphology of neurons in the medial entorhinal cortex of 3-mo-old TR mice, neurons important to spatial learning functions. We found significantly shorter dendrites and lower spine densities in basal shaft dendrites of E4 mice compared to E3 mice, consistent with spatial learning and memory deficits in E4 animals. These findings suggest that human <jats:italic>APOE-\u03b54<\/jats:italic> may affect cognitive function and neuronal morphology early in life.<\/jats:p>","DOI":"10.1101\/lm.030031.112","type":"journal-article","created":{"date-parts":[[2013,4,17]],"date-time":"2013-04-17T05:22:49Z","timestamp":1366176169000},"page":"256-266","source":"Crossref","is-referenced-by-count":128,"title":["Young APOE4 targeted replacement mice exhibit poor spatial learning and memory, with reduced dendritic spine density in the medial entorhinal cortex"],"prefix":"10.1101","volume":"20","author":[{"given":"Gustavo A.","family":"Rodriguez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P.","family":"Burns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin J.","family":"Weeber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. William","family":"Rebeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2013,4,16]]},"reference":[{"key":"2021111206254573000_20.5.256.1","doi-asserted-by":"publisher","DOI":"10.1159\/000093129"},{"key":"2021111206254573000_20.5.256.2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4040-10.2010"},{"key":"2021111206254573000_20.5.256.3","doi-asserted-by":"publisher","DOI":"10.1037\/h0077579"},{"key":"2021111206254573000_20.5.256.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(98)00008-3"},{"key":"2021111206254573000_20.5.256.5","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.390"},{"key":"2021111206254573000_20.5.256.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.05.008"},{"key":"2021111206254573000_20.5.256.7","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(95)00021-6"},{"key":"2021111206254573000_20.5.256.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109038108"},{"key":"2021111206254573000_20.5.256.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2008.03.039"},{"key":"2021111206254573000_20.5.256.10","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19980216)391:3<293::AID-CNE2>3.0.CO;2-X"},{"key":"2021111206254573000_20.5.256.11","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20993"},{"key":"2021111206254573000_20.5.256.12","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/381243"},{"key":"2021111206254573000_20.5.256.13","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.1.201"},{"key":"2021111206254573000_20.5.256.14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0809437"},{"key":"2021111206254573000_20.5.256.15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914984107"},{"key":"2021111206254573000_20.5.256.16","first-page":"13","article-title":"Tuning synaptic transmission in the hippocampus by stress: The CRH system","volume":"6","year":"2012","journal-title":"Front Cell Neurosci"},{"key":"2021111206254573000_20.5.256.17","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"2021111206254573000_20.5.256.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.06.009"},{"key":"2021111206254573000_20.5.256.19","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4026-09.2009"},{"key":"2021111206254573000_20.5.256.20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2012.07908.x"},{"key":"2021111206254573000_20.5.256.21","doi-asserted-by":"crossref","first-page":"4491","DOI":"10.1523\/JNEUROSCI.16-14-04491.1996","article-title":"Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer\u2019s disease","volume":"16","year":"1996","journal-title":"J Neurosci"},{"key":"2021111206254573000_20.5.256.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2004.09.019"},{"key":"2021111206254573000_20.5.256.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.10.015"},{"key":"2021111206254573000_20.5.256.24","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4872-08.2009"},{"key":"2021111206254573000_20.5.256.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2010.04.004"},{"key":"2021111206254573000_20.5.256.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.05.048"},{"key":"2021111206254573000_20.5.256.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.06.026"},{"key":"2021111206254573000_20.5.256.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2004.07.084"},{"key":"2021111206254573000_20.5.256.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(03)00171-9"},{"key":"2021111206254573000_20.5.256.30","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-4-21"},{"key":"2021111206254573000_20.5.256.31","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5293.1678"},{"key":"2021111206254573000_20.5.256.32","doi-asserted-by":"publisher","DOI":"10.1037\/0894-4105.20.6.645"},{"key":"2021111206254573000_20.5.256.33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0048895"},{"key":"2021111206254573000_20.5.256.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2011.09.027"},{"key":"2021111206254573000_20.5.256.35","unstructured":"Paxinos G , Franklin KBJ . 2001. The mouse brain in stereotaxic coordinates. Academic Press, San Diego, CA."},{"key":"2021111206254573000_20.5.256.36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1327-10.2010"},{"key":"2021111206254573000_20.5.256.37","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/35006165","article-title":"Apolipoprotein E and cognitive performance","volume":"404","year":"2000","journal-title":"Nature"},{"key":"2021111206254573000_20.5.256.38","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1467"},{"key":"2021111206254573000_20.5.256.39","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"2021111206254573000_20.5.256.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2012.06.020"},{"key":"2021111206254573000_20.5.256.41","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70106-0"},{"key":"2021111206254573000_20.5.256.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.03.002"},{"key":"2021111206254573000_20.5.256.43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.5.1977"},{"key":"2021111206254573000_20.5.256.44","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.29.17972"},{"key":"2021111206254573000_20.5.256.45","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200412030-00020"},{"key":"2021111206254573000_20.5.256.46","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.10037"},{"key":"2021111206254573000_20.5.256.47","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1176\/jnp.9.3.331","article-title":"Ventromedial temporal lobe anatomy, with comments on Alzheimer\u2019s disease and temporal injury","volume":"9","year":"1997","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"2021111206254573000_20.5.256.48","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.450010102"},{"key":"2021111206254573000_20.5.256.49","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2614"},{"key":"2021111206254573000_20.5.256.50","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70325-2"},{"key":"2021111206254573000_20.5.256.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.10.013"},{"key":"2021111206254573000_20.5.256.52","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2012.2456"},{"key":"2021111206254573000_20.5.256.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2006.10.003"},{"key":"2021111206254573000_20.5.256.54","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0022-2275(20)38094-9","article-title":"Proposed nomenclature of ApoE isoproteins, ApoE genotypes, and phenotypes","volume":"23","year":"1982","journal-title":"J Lipid Res"}],"container-title":["Learning &amp; Memory"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/lm.030031.112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T14:26:26Z","timestamp":1636727186000},"score":1,"resource":{"primary":{"URL":"http:\/\/learnmem.cshlp.org\/lookup\/doi\/10.1101\/lm.030031.112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,16]]},"references-count":54,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2013,4,16]]},"published-print":{"date-parts":[[2013,5]]}},"alternative-id":["10.1101\/lm.030031.112"],"URL":"https:\/\/doi.org\/10.1101\/lm.030031.112","relation":{},"ISSN":["1549-5485"],"issn-type":[{"value":"1549-5485","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,16]]}}}