{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:43:50Z","timestamp":1792532630370,"version":"4.5.0"},"reference-count":78,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T00:00:00Z","timestamp":1697760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Foundation-Flanders (FWO)"},{"name":"Medical Research Foundation Antwerp"},{"name":"Thomas Riellaerts research fund"},{"name":"Neurosearch Antwerp"},{"name":"Belgian Alzheimer Research Foundation (SAO-FRA)"},{"name":"University of Antwerp"},{"name":"University Medical Center Groningen"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: The Tau58\/2 and Tau58\/4 mouse lines expressing 0N4R tau with a P301S mutation mimic aspects of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). In a side-by-side comparison, we report the age-dependent development of cognitive, motor, and behavioral deficits in comparison with the spatial-temporal evolution of cellular tau pathology in both models. Methods: We applied the SHIRPA primary screen and specific neuromotor, behavioral, and cognitive paradigms. The spatiotemporal development of tau pathology was investigated immunohistochemically. Levels of sarkosyl-insoluble paired helical filaments were determined via a MesoScale Discovery biomarker assay. Results: Neuromotor impairments developed from age 3 months in both models. On electron microscopy, spinal cord neurofibrillary pathology was visible in mice aged 3 months; however, AT8 immunoreactivity was not yet observed in Tau58\/4 mice. Behavioral abnormalities and memory deficits occurred at a later stage (&gt;9 months) when tau pathology was fully disseminated throughout the brain. Spatiotemporally, tau pathology spread from the spinal cord via the midbrain to the frontal cortex, while the hippocampus was relatively spared, thus explaining the late onset of cognitive deficits. Conclusions: Our findings indicate the face and construct validity of both Tau58 models, which may provide new, valuable insights into the pathologic effects of tau species in vivo and may consequently facilitate the development of new therapeutic targets to delay or halt neurodegenerative processes occurring in tauopathies.<\/jats:p>","DOI":"10.3390\/life13102088","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T07:22:32Z","timestamp":1697786552000},"page":"2088","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Behavioral and Neuropathological Phenotyping of the Tau58\/2 and Tau58\/4 Transgenic Mouse Models for FTDP-17"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4739-6076","authenticated-orcid":false,"given":"Debby","family":"Van Dam","sequence":"first","affiliation":[{"name":"Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, University of Antwerp, Wilrijk, 2610 Antwerp, Belgium"},{"name":"Department of Neurology and Alzheimer Center Groningen, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke","family":"Valkenburg","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, University of Antwerp, Wilrijk, 2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristof","family":"Van Kolen","sequence":"additional","affiliation":[{"name":"Neuroscience Department, Janssen Research and Development, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Pintelon","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2506-6252","authenticated-orcid":false,"given":"Jean-Pierre","family":"Timmermans","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2228-2964","authenticated-orcid":false,"given":"Peter Paul","family":"De Deyn","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, University of Antwerp, Wilrijk, 2610 Antwerp, Belgium"},{"name":"Department of Neurology and Alzheimer Center Groningen, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00401-007-0291-9","article-title":"Tauopathy models and human neuropathology: Similarities and differences","volume":"115","author":"Frank","year":"2008","journal-title":"Acta Neuropathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/S1474-4422(13)70090-5","article-title":"Tau pathology and neurodegeneration","volume":"12","author":"Spillantini","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3708","DOI":"10.1093\/brain\/awr308","article-title":"Neocortical and hippocampal amyloid-B and tau measures associate with dementia in the oldest-old","volume":"134","author":"Robinson","year":"2011","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/NEN.0b013e3181919a48","article-title":"Neuropathology and Cognitive Impairment in Alzheimer Disease: A Complex but Coherent Relationship","volume":"68","author":"Nelson","year":"2009","journal-title":"J. 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