Martina Laczó, Zuzana Svacova, Ondrej Lerch, Lukas Martinkovic, Monika Krejci, Zuzana Nedelska, Hana Horakova, Vaclav Matoska, Martin Vyhnalek, Jakub Hort, Michael Hornberger, Jan Laczó
{"title":"早期阿尔茨海默病的空间导航缺陷：生物标志物和APOE基因型的作用","authors":"Martina Laczó, Zuzana Svacova, Ondrej Lerch, Lukas Martinkovic, Monika Krejci, Zuzana Nedelska, Hana Horakova, Vaclav Matoska, Martin Vyhnalek, Jakub Hort, Michael Hornberger, Jan Laczó","doi":"10.1007/s00415-025-13151-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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-β<sub>1-42</sub>, phosphorylated tau<sub>181</sub> and total tau) and amyloid PET imaging were assessed in aMCI participants.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"438"},"PeriodicalIF":4.6000,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130088/pdf/","citationCount":"0","resultStr":"{\"title\":\"Spatial navigation deficits in early Alzheimer's disease: the role of biomarkers and APOE genotype.\",\"authors\":\"Martina Laczó, Zuzana Svacova, Ondrej Lerch, Lukas Martinkovic, Monika Krejci, Zuzana Nedelska, Hana Horakova, Vaclav Matoska, Martin Vyhnalek, Jakub Hort, Michael Hornberger, Jan Laczó\",\"doi\":\"10.1007/s00415-025-13151-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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-β<sub>1-42</sub>, phosphorylated tau<sub>181</sub> and total tau) and amyloid PET imaging were assessed in aMCI participants.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":16558,\"journal\":{\"name\":\"Journal of Neurology\",\"volume\":\"272 6\",\"pages\":\"438\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-06-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130088/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00415-025-13151-8\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00415-025-13151-8","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Spatial navigation deficits in early Alzheimer's disease: the role of biomarkers and APOE genotype.
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.
期刊介绍：
The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field.
In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials.
Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.
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