{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T03:10:23Z","timestamp":1772507423087,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Before the course of Alzheimer\u2019s disease fully manifests itself and largely impairs a patient\u2019s cognitive abilities, its progression has already lasted for a considerable time without being noticed. In this project, we mapped the development of spatial orientation impairment in an active place avoidance task\u2014a highly sensitive test for mild hippocampal damage. We tested vision, anxiety and spatial orientation performance at four age levels of 4, 6, 9, and 12 months across male and female TgF-344 AD rats carrying human genes for presenilin-1 and amyloid precursor protein. We found a progressive deterioration of spatial navigation in transgenic animals, beginning already at the age of 4 months, that fully developed at 6 months of age across both male and female groups, compared to their age-matched controls. In addition, we described the gradual vision impairment that was accentuated in females at the age of 12 months. These results indicate a rather early onset of cognitive impairment in the TgF-344 AD Alzheimer\u2019s disease model, starting earlier than shown to date, and preceding the reported development of amyloid plaques.<\/jats:p>","DOI":"10.3390\/brainsci11101300","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T10:22:42Z","timestamp":1632997362000},"page":"1300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Early Spatial Memory Impairment in a Double Transgenic Model of Alzheimer\u2019s Disease TgF-344 AD"],"prefix":"10.3390","volume":"11","author":[{"given":"Stephanie L.","family":"Proskauer Pena","sequence":"first","affiliation":[{"name":"Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 30605 Pilsen, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantinos","family":"Mallouppas","sequence":"additional","affiliation":[{"name":"Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 30605 Pilsen, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre M. G.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 30605 Pilsen, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frantisek","family":"Zitricky","sequence":"additional","affiliation":[{"name":"Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 30605 Pilsen, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athira","family":"Nataraj","sequence":"additional","affiliation":[{"name":"Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 30605 Pilsen, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karel","family":"Jezek","sequence":"additional","affiliation":[{"name":"Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 30605 Pilsen, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1056\/NEJMra0909142","article-title":"Alzheimer\u2019s Disease","volume":"362","author":"Querfurth","year":"2010","journal-title":"N. 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