BACKGROUND: Spatial navigation deficits are early symptoms of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for AD. This study investigated effects of APOE 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. METHODS: 107 participants, cognitively normal older adults (CN, n = 48) and aMCI individuals stratified into AD aMCI (n = 28) and non-AD aMCI (n = 31) 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-β1-42, phosphorylated tau181 and total tau) and amyloid PET imaging were assessed in aMCI participants. RESULTS: AD aMCI participants had the highest prevalence of APOE ε4 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 APOE genotype. Self-reported navigation ability was similar across groups and unrelated to spatial navigation performance. CONCLUSIONS: These findings suggest that allocentric navigation deficits in aMCI individuals are predominantly driven by AD pathology, independent of APOE 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.

• Klíčová slova
• Allocentric navigation, Amyloid-β, Egocentric navigation, Entorhinal cortex, Hippocampus, Tau protein,
• MeSH
• Alzheimerova nemoc * genetika   mozkomíšní mok   diagnostické zobrazování   komplikace   patofyziologie   patologie   MeSH
• amyloidní beta-protein mozkomíšní mok   MeSH
• apolipoprotein E4 * genetika   MeSH
• apolipoproteiny E * genetika   MeSH
• atrofie MeSH
• biologické markery mozkomíšní mok   MeSH
• genotyp MeSH
• kognitivní dysfunkce * genetika   mozkomíšní mok   diagnostické zobrazování   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   diagnostické zobrazování   MeSH
• neuropsychologické testy MeSH
• peptidové fragmenty mozkomíšní mok   MeSH
• pozitronová emisní tomografie MeSH
• prostorová navigace * fyziologie   MeSH
• proteiny tau mozkomíšní mok   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amyloid beta-protein (1-42) MeSH Prohlížeč
• amyloidní beta-protein MeSH
• apolipoprotein E4 * MeSH
• apolipoproteiny E * MeSH
• biologické markery MeSH
• peptidové fragmenty MeSH
• proteiny tau MeSH