{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T04:09:51Z","timestamp":1791691791332,"version":"4.3.4"},"reference-count":80,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T00:00:00Z","timestamp":1440633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005357","name":"Slovak Research and Development Agency","doi-asserted-by":"crossref","award":["APVV 0206-11"],"award-info":[{"award-number":["APVV 0206-11"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005357","name":"Slovak Research and Development Agency","doi-asserted-by":"crossref","award":["APVV 0200-11"],"award-info":[{"award-number":["APVV 0200-11"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005357","name":"Slovak Research and Development Agency","doi-asserted-by":"crossref","award":["APVV 0677-12"],"award-info":[{"award-number":["APVV 0677-12"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"crossref"}]},{"name":"EU Structural Fund","award":["26240220046"],"award-info":[{"award-number":["26240220046"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Canine cognitive impairment syndrome (CDS) represents a group of symptoms related to the aging of the canine brain. These changes ultimately lead to a decline of memory function and learning abilities, alteration of social interaction, impairment of normal housetraining, and changes in sleep\u2013wake cycle and general activity. We have clinically examined 215 dogs, 28 of which underwent autopsy. With canine brains, we performed extensive analysis of pathological abnormalities characteristic of human Alzheimer's disease and frontotemporal lobar degeneration, including \u03b2\u2010amyloid senile plaques, tau neurofibrillary tangles, and fused in sarcoma (FUS) and TAR DNA\u2010binding protein 43 (TDP43) inclusions. Most demented dogs displayed senile plaques, mainly in the frontal and temporal cortex. Tau neurofibrillary inclusions were found in only one dog. They were identified with antibodies used to detect tau neurofibrillary lesions in the human brain. The inclusions were also positive for Gallyas silver staining. As in humans, they were distributed mainly in the entorhinal cortex, hippocampus, and temporal cortex. On the other hand, FUS and TDP43 aggregates were not present in any of the examined brain samples. We also found that CDS was characterized by the presence of reactive and senescent microglial cells in the frontal cortex. Our transcriptomic study revealed a significant dysregulation of genes involved in neuroinflammation. Finally, we analyzed tau phosphoproteome in the synaptosomes. Proteomic studies revealed a significant increase of hyperphosphorylated tau in synaptosomes of demented dogs compared with nondemented dogs. This study suggests that cognitive decline in dogs is related to the tau synaptic impairment and neuroinflammation. J. Comp. Neurol. 524:874\u2013895, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/cne.23877","type":"journal-article","created":{"date-parts":[[2015,8,3]],"date-time":"2015-08-03T19:21:16Z","timestamp":1438629676000},"page":"874-895","source":"Crossref","is-referenced-by-count":67,"title":["Tau hyperphosphorylation in synaptosomes and neuroinflammation are associated with canine cognitive impairment"],"prefix":"10.1002","volume":"524","author":[{"given":"Tomas","family":"Smolek","sequence":"first","affiliation":[{"name":"Institute of Neuroimmunology, Slovak Academy of Sciences 845 10 Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aladar","family":"Madari","sequence":"additional","affiliation":[{"name":"University of Veterinary Medicine and Pharmacy 040 01 Kosice Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Farbakova","sequence":"additional","affiliation":[{"name":"University of Veterinary Medicine and Pharmacy 040 01 Kosice Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondrej","family":"Kandrac","sequence":"additional","affiliation":[{"name":"University of Veterinary Medicine and Pharmacy 040 01 Kosice Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh","family":"Jadhav","sequence":"additional","affiliation":[{"name":"Institute of Neuroimmunology, Slovak Academy of Sciences 845 10 Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Cente","sequence":"additional","affiliation":[{"name":"Institute of Neuroimmunology, Slovak Academy of Sciences 845 10 Bratislava Slovak Republic"},{"name":"Axon Neuroscience SE 811 02 Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Brezovakova","sequence":"additional","affiliation":[{"name":"Institute of Neuroimmunology, Slovak Academy of Sciences 845 10 Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Novak","sequence":"additional","affiliation":[{"name":"Institute of Neuroimmunology, Slovak Academy of Sciences 845 10 Bratislava Slovak Republic"},{"name":"Axon Neuroscience SE 811 02 Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Zilka","sequence":"additional","affiliation":[{"name":"Institute of Neuroimmunology, Slovak Academy of Sciences 845 10 Bratislava Slovak Republic"},{"name":"Axon Neuroscience SE 811 02 Bratislava Slovak Republic"},{"name":"Institute of Neuroimmunology n.o., 811 02 Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,8,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2008.00147.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010100423"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(83)90036-2"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1354\/vp.36-3-202"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90589-4"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2010.08.088"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2012.04.009"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.74.1.181"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2003.09.001"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00113-5"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-198811000-00006"},{"key":"e_1_2_8_14_1","first-page":"15","volume-title":"Handbook of animal models in Alzheimer's disease","author":"Cotman CW","year":"2011"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-200606000-00007"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(95)02060-8"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.02.017"},{"key":"e_1_2_8_18_1","first-page":"5","article-title":"Prevention approaches in a preclinical canine model of Alzheimer's disease: benefits and challenges","volume":"21","author":"Davis PR","year":"2014","journal-title":"Front Pharmacol"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-4541-9"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.10.015"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2015.00009"},{"key":"e_1_2_8_22_1","first-page":"1","article-title":"Silver staining of Alzheimer's neurofibrillary changes by means of physical development","volume":"19","author":"Gallyas F","year":"1971","journal-title":"Acta Morphol Acad Sci Hung"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(90)90068-K"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0940-9602(01)80236-3"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfms.2006.01.003"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010000183"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(98)00084-0"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00093-2"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2004.06.015"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.10.001"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1159\/000008108"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2003.04.005"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199703030-00038"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9584-6"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.07.027"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00024"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(99)00079-0"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(91)90088-F"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0839-6"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109218200"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt277"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cvsm.2004.12.008"},{"key":"e_1_2_8_43_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cvsm.2012.04.003","article-title":"Cognitive dysfunction syndrome: a disease of canine and feline brain aging","volume":"42","author":"Landsberg GM","year":"2012","journal-title":"Vet Clin North Am Small Anim Pract"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2008-15112"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.02.012"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-007-0273-y"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.1.127"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.401240"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199409080-00035"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90270-4"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp214"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00296186"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.applanim.2006.11.007"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.3109\/13506120108993810"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20223"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0087-3"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(95)02069-1"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.3109\/13506120309041730"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.11.021"},{"key":"e_1_2_8_60_1","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1097\/00001756-199212000-00015","article-title":"Familial influence on plaque formation in the beagle brain","volume":"3","author":"Russell M","year":"1992","journal-title":"Neuroreport"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(95)02072-1"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000260698.46517.8f"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(91)90712-3"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.09.018"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-7-64"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2006.07.001"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(98)00069-0"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0556-6"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.06.033"},{"key":"e_1_2_8_70_1","first-page":"146","article-title":"Frequent and symmetric deposition of misfolded tau oligomers within presynaptic and postsynaptic terminals in Alzheimer's disease","volume":"2","author":"Tai HC","year":"2014","journal-title":"Acta Neuropathol Commun"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1339-04.2004"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.54.659"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.54.1023"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.55.637"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200301200-00017"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05190.x"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3418-14.2014"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(96)00373-3"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004447"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1177\/030098589603300214"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcpa.2010.11.004"}],"container-title":["Journal of Comparative Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcne.23877","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cne.23877","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T20:12:17Z","timestamp":1696623137000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cne.23877"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,27]]},"references-count":80,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1002\/cne.23877"],"URL":"https:\/\/doi.org\/10.1002\/cne.23877","archive":["Portico"],"relation":{},"ISSN":["0021-9967","1096-9861"],"issn-type":[{"value":"0021-9967","type":"print"},{"value":"1096-9861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,27]]}}}