{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:31:27Z","timestamp":1787319087766,"version":"build-2736575974"},"reference-count":63,"publisher":"Society for Neuroscience","issue":"50","license":[{"start":{"date-parts":[[2018,6,13]],"date-time":"2018-06-13T00:00:00Z","timestamp":1528848000000},"content-version":"vor","delay-in-days":223,"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":[[2017,12,13]]},"abstract":"<jats:p>\n                    Imaging biomarkers are frequently proposed as endpoints for clinical trials targeting brain amyloidosis in Alzheimer's disease (AD); however, the specific impact of amyloid-\u03b2 (A\u03b2) aggregation on biomarker abnormalities remains elusive in AD. Using the McGill-R-Thy1-APP transgenic rat as a model of selective A\u03b2 pathology, we characterized the longitudinal progression of abnormalities in biomarkers commonly used in AD research. Middle-aged (9\u201311 months) transgenic animals (both male and female) displayed mild spatial memory impairments and disrupted cingulate network connectivity measured by resting-state fMRI, even in the absence of hypometabolism (measured with PET [\n                    <jats:sup>18<\/jats:sup>\n                    F]FDG) or detectable fibrillary amyloidosis (measured with PET [\n                    <jats:sup>18<\/jats:sup>\n                    F]NAV4694). At more advanced ages (16\u201319 months), cognitive deficits progressed in conjunction with resting connectivity abnormalities; furthermore, hypometabolism, A\u03b2 plaque accumulation, reduction of CSF A\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    concentrations, and hippocampal atrophy (structural MRI) were detectable at this stage. The present results emphasize the early impact of A\u03b2 on brain connectivity and support a framework in which persistent A\u03b2 aggregation itself is sufficient to impose memory circuits dysfunction, which propagates to adjacent brain networks at later stages.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>\n                    The present study proposes a \u201cback translation\u201d of the Alzheimer pathological cascade concept from human to animals. We used the same set of Alzheimer imaging biomarkers typically used in large human cohorts and assessed their progression over time in a transgenic rat model, which allows for a finer spatial resolution not attainable with mice. Using this translational platform, we demonstrated that amyloid-\u03b2 pathology recapitulates an Alzheimer-like profile of biomarker abnormalities even in the absence of other hallmarks of the disease such as neurofibrillary tangles and widespread neuronal losses.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.1346-17.2017","type":"journal-article","created":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T12:55:32Z","timestamp":1513169732000},"page":"12263-12271","source":"Crossref","is-referenced-by-count":44,"title":["Multimodal Imaging in Rat Model Recapitulates Alzheimer's Disease Biomarkers Abnormalities"],"prefix":"10.1523","volume":"37","author":[{"given":"Maxime J.","family":"Parent","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5349-0053","authenticated-orcid":false,"given":"Eduardo R.","family":"Zimmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2527-5636","authenticated-orcid":false,"given":"Monica","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Su","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3402-7749","authenticated-orcid":false,"given":"Vladimir S.","family":"Fonov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Mathieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Aliaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1646-761X","authenticated-orcid":false,"given":"Alexey","family":"Kostikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Do Carmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Dea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8018-4545","authenticated-orcid":false,"given":"Judes","family":"Poirier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6979-1259","authenticated-orcid":false,"given":"Jean-Paul","family":"Soucy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Gauthier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Claudio","family":"Cuello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9116-1376","authenticated-orcid":false,"given":"Pedro","family":"Rosa-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2017,11,2]]},"reference":[{"key":"2023041803283435000_37.50.12263.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5562"},{"key":"2023041803283435000_37.50.12263.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.09.028"},{"key":"2023041803283435000_37.50.12263.3","doi-asserted-by":"crossref","first-page":"825.e1","DOI":"10.1016\/j.neurobiolaging.2011.05.003","article-title":"Different beta-amyloid oligomer assemblies in Alzheimer brains correlate with age of disease onset and impaired cholinergic activity","volume":"33","author":"Bao","year":"2012","journal-title":"Neurobiol Aging"},{"key":"2023041803283435000_37.50.12263.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1202753"},{"key":"2023041803283435000_37.50.12263.5","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1523\/JNEUROSCI.22-02-00515.2002","article-title":"Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice","volume":"22","author":"Bondolfi","year":"2002","journal-title":"J Neurosci"},{"key":"2023041803283435000_37.50.12263.6","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.155"},{"key":"2023041803283435000_37.50.12263.7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2177-05.2005"},{"key":"2023041803283435000_37.50.12263.8","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1440.011"},{"key":"2023041803283435000_37.50.12263.9","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5062-08.2009"},{"key":"2023041803283435000_37.50.12263.10","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2250-06.2006"},{"key":"2023041803283435000_37.50.12263.11","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.111.094029"},{"key":"2023041803283435000_37.50.12263.12","doi-asserted-by":"publisher","DOI":"10.2174\/138161208784705487"},{"key":"2023041803283435000_37.50.12263.13","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199704000-00001"},{"key":"2023041803283435000_37.50.12263.14","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-8-37"},{"key":"2023041803283435000_37.50.12263.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.02.002"},{"key":"2023041803283435000_37.50.12263.16","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3806"},{"key":"2023041803283435000_37.50.12263.17","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1353-14.2014"},{"key":"2023041803283435000_37.50.12263.18","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3389\/fnbeh.2014.00321","article-title":"Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer's disease","volume":"8","author":"Galeano","year":"2014","journal-title":"Front Behav Neurosci"},{"key":"2023041803283435000_37.50.12263.19","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-142547"},{"key":"2023041803283435000_37.50.12263.20","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(84)91209-9"},{"key":"2023041803283435000_37.50.12263.21","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90117-V"},{"key":"2023041803283435000_37.50.12263.22","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2000-23-403"},{"key":"2023041803283435000_37.50.12263.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308627101"},{"key":"2023041803283435000_37.50.12263.24","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.1016\/S0021-9258(17)38495-8","article-title":"Microtubule-associated protein tau. A component of Alzheimer paired helical filaments","volume":"261","author":"Grundke-Iqbal","year":"1986","journal-title":"J Biol Chem"},{"key":"2023041803283435000_37.50.12263.25","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.1997.0303"},{"key":"2023041803283435000_37.50.12263.26","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3189-09.2009"},{"key":"2023041803283435000_37.50.12263.27","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12876"},{"key":"2023041803283435000_37.50.12263.28","doi-asserted-by":"publisher","DOI":"10.1186\/2051-5960-2-61"},{"key":"2023041803283435000_37.50.12263.29","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70299-6"},{"key":"2023041803283435000_37.50.12263.30","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.183"},{"key":"2023041803283435000_37.50.12263.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.12.003"},{"key":"2023041803283435000_37.50.12263.32","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv326"},{"key":"2023041803283435000_37.50.12263.33","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.4668"},{"key":"2023041803283435000_37.50.12263.34","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1523\/JNEUROSCI.21-02-00372.2001","article-title":"Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease","volume":"21","author":"Kawarabayashi","year":"2001","journal-title":"J Neurosci"},{"key":"2023041803283435000_37.50.12263.35","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.8.1188"},{"key":"2023041803283435000_37.50.12263.36","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20009"},{"key":"2023041803283435000_37.50.12263.37","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(88)90129-8"},{"key":"2023041803283435000_37.50.12263.38","doi-asserted-by":"publisher","DOI":"10.1007\/s11307-009-0198-z"},{"key":"2023041803283435000_37.50.12263.39","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3501-06.2007"},{"key":"2023041803283435000_37.50.12263.40","first-page":"929","article-title":"Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease","volume":"15","author":"Leh\u00e9ricy","year":"1994","journal-title":"AJNR Am J Neuroradiol"},{"key":"2023041803283435000_37.50.12263.41","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-1349"},{"key":"2023041803283435000_37.50.12263.42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200506109"},{"key":"2023041803283435000_37.50.12263.43","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0673-07.2007"},{"key":"2023041803283435000_37.50.12263.44","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(89)90582-X"},{"key":"2023041803283435000_37.50.12263.45","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.1002\/j.1460-2075.1985.tb04000.x","article-title":"Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels","volume":"4","author":"Masters","year":"1985","journal-title":"EMBO J"},{"key":"2023041803283435000_37.50.12263.46","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/122.8.1519"},{"key":"2023041803283435000_37.50.12263.47","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410420114"},{"key":"2023041803283435000_37.50.12263.48","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(84)90007-4"},{"key":"2023041803283435000_37.50.12263.49","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9861(20001106)427:1<19::AID-CNE2>3.0.CO;2-A"},{"key":"2023041803283435000_37.50.12263.50","first-page":"P499","article-title":"Resting-state connectivity impairment in a rat model of Alzheimer's disease","volume":"9","author":"Parent","year":"2013","journal-title":"Alzheimers Dement"},{"key":"2023041803283435000_37.50.12263.51","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-014-0175-x"},{"key":"2023041803283435000_37.50.12263.52","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1152\/physrev.2001.81.2.741","article-title":"Alzheimer's disease: genes, proteins, and therapy","volume":"81","author":"Selkoe","year":"2001","journal-title":"Physiol Rev"},{"key":"2023041803283435000_37.50.12263.53","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10498"},{"key":"2023041803283435000_37.50.12263.54","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.17.2120"},{"key":"2023041803283435000_37.50.12263.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"2023041803283435000_37.50.12263.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.07.003"},{"key":"2023041803283435000_37.50.12263.57","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000046581.81650.D0"},{"key":"2023041803283435000_37.50.12263.58","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-005-1780-5"},{"key":"2023041803283435000_37.50.12263.59","doi-asserted-by":"publisher","DOI":"10.1038\/416535a"},{"key":"2023041803283435000_37.50.12263.60","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhv332"},{"key":"2023041803283435000_37.50.12263.61","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0193(1996)4:1<58::AID-HBM4>3.0.CO;2-O"},{"key":"2023041803283435000_37.50.12263.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2014.07.002"},{"key":"2023041803283435000_37.50.12263.63","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4492"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.1346-17.2017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T07:10:17Z","timestamp":1681801817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.1346-17.2017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,2]]},"references-count":63,"journal-issue":{"issue":"50","published-online":{"date-parts":[[2017,12,13]]},"published-print":{"date-parts":[[2017,12,13]]}},"alternative-id":["10.1523\/JNEUROSCI.1346-17.2017"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.1346-17.2017","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,2]]}}}