{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:51:14Z","timestamp":1792111874334,"version":"4.4.0"},"reference-count":69,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T00:00:00Z","timestamp":1543881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG047589"],"award-info":[{"award-number":["R01AG047589"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A variety of Alzheimer's disease (AD) mouse models overexpress mutant forms of human amyloid precursor protein (APP), producing high levels of amyloid \u03b2 (A\u03b2) and forming plaques. However, the degree to which these models mimic spatiotemporal patterns of A\u03b2 deposition in brains of AD patients is unknown. Here, we mapped the spatial distribution of A\u03b2 plaques across age in three APP\u2010overexpression mouse lines (APP\/PS1, Tg2576, and hAPP\u2010J20) using in vivo labeling with methoxy\u2010X04, high throughput whole brain imaging, and an automated informatics pipeline. Images were acquired with high resolution serial two\u2010photon tomography and labeled plaques were detected using custom\u2010built segmentation algorithms. Image series were registered to the Allen Mouse Brain Common Coordinate Framework, a 3D reference atlas, enabling automated brain\u2010wide quantification of plaque density, number, and location. In both APP\/PS1 and Tg2576 mice, plaques were identified first in isocortex, followed by olfactory, hippocampal, and cortical subplate areas. In hAPP\u2010J20 mice, plaque density was highest in hippocampal areas, followed by isocortex, with little to no involvement of olfactory or cortical subplate areas. Within the major brain divisions, distinct regions were identified with high (or low) plaque accumulation; for example, the lateral visual area within the isocortex of APP\/PS1 mice had relatively higher plaque density compared with other cortical areas, while in hAPP\u2010J20 mice, plaques were densest in the ventral retrosplenial cortex. In summary, we show how whole brain imaging of amyloid pathology in mice reveals the extent to which a given model recapitulates the regional A\u03b2 deposition patterns described in AD.<\/jats:p>","DOI":"10.1002\/cne.24555","type":"journal-article","created":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T05:36:58Z","timestamp":1539322618000},"page":"2122-2145","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease"],"prefix":"10.1002","volume":"527","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2961-5207","authenticated-orcid":false,"given":"Jennifer D.","family":"Whitesell","sequence":"first","affiliation":[{"name":"Allen Institute for Brain Science  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex R.","family":"Buckley","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Knox","sequence":"additional","affiliation":[{"name":"Allen Institute for Brain Science  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Kuan","sequence":"additional","affiliation":[{"name":"Allen Institute for Brain Science  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nile","family":"Graddis","sequence":"additional","affiliation":[{"name":"Allen Institute for Brain Science  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Pelos","sequence":"additional","affiliation":[{"name":"Allen Institute for Brain Science  Seattle Washington"},{"name":"Department of Neuroscience Pomona College  Claremont California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Mukora","sequence":"additional","affiliation":[{"name":"Allen Institute for Brain Science  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne","family":"Wakeman","sequence":"additional","affiliation":[{"name":"Allen Institute for Brain Science  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Bohn","sequence":"additional","affiliation":[{"name":"Allen Institute for Brain Science  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh","family":"Ho","sequence":"additional","affiliation":[{"name":"Allen Institute for Brain Science  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla E.","family":"Hirokawa","sequence":"additional","affiliation":[{"name":"Allen Institute for Brain Science  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0820-2021","authenticated-orcid":false,"given":"Julie A.","family":"Harris","sequence":"additional","affiliation":[{"name":"Allen Institute for Brain Science  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2801"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0127-z"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116678"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5698-11.2012"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2177-05.2005"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1440.011"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.02.003"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep00019"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-016-0481-z"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00261-X"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1981.tb01789.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.08.017"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004643"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2011.07.008"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2011.11.017"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.10.020"},{"key":"e_1_2_7_19_1","article-title":"The organization of intracortical connections by layer and cell class in the mouse brain","author":"Harris J. 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