{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:03:40Z","timestamp":1790960620207,"version":"4.1.0"},"reference-count":100,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Spatial navigation deficits are early symptoms of Alzheimer\u2019s disease (AD). The apolipoprotein E (<jats:italic>APOE<\/jats:italic>) \u03b54 allele is the most important genetic risk factor for AD. This study investigated effects of <jats:italic>APOE<\/jats:italic> genotype on spatial navigation in biomarker-defined individuals with amnestic mild cognitive impairment (aMCI) and associations of AD biomarkers and atrophy of AD-related brain regions with spatial navigation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>107 participants, cognitively normal older adults (CN, <jats:italic>n<\/jats:italic>\u2009=\u200948) and aMCI individuals stratified into AD aMCI (<jats:italic>n<\/jats:italic>\u2009=\u200928) and non-AD aMCI (<jats:italic>n<\/jats:italic>\u2009=\u200931) groups, underwent cognitive assessment, brain MRI, and spatial navigation assessment using the Virtual Supermarket Test with egocentric and allocentric tasks and a self-report questionnaire. Cerebrospinal fluid (CSF) biomarkers (amyloid-\u03b2<jats:sub>1\u201342<\/jats:sub>, phosphorylated tau<jats:sub>181<\/jats:sub> and total tau) and amyloid PET imaging were assessed in aMCI participants.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>AD aMCI participants had the highest prevalence of <jats:italic>APOE<\/jats:italic> \u03b54 carriers and worst allocentric navigation. CSF levels of AD biomarkers and atrophy in AD-related brain regions were associated with worse allocentric navigation. Between-group differences in spatial navigation and associations with AD biomarkers and regional brain atrophy were not influenced by <jats:italic>APOE<\/jats:italic> genotype. Self-reported navigation ability was similar across groups and unrelated to spatial navigation performance.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These findings suggest that allocentric navigation deficits in aMCI individuals are predominantly driven by AD pathology, independent of <jats:italic>APOE<\/jats:italic> genotype. This highlights the role of AD pathology as measured by biomarkers, rather than genetic status, as a major factor in navigational impairment in aMCI, and emphasizes the assessment of spatial navigation as a valuable tool for early detection of AD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00415-025-13151-8","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T15:22:28Z","timestamp":1748877748000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Spatial navigation deficits in early Alzheimer\u2019s disease: the role of biomarkers and APOE genotype"],"prefix":"10.1007","volume":"272","author":[{"given":"Martina","family":"Lacz\u00f3","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Svacova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondrej","family":"Lerch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Martinkovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Krejci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Nedelska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Horakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaclav","family":"Matoska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Vyhnalek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Hort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hornberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lacz\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"13151_CR1","doi-asserted-by":"publisher","unstructured":"(2023) 2023 Alzheimer\u2019s disease facts and figures. 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