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. 2025 Jun 2;272(6):438.
doi: 10.1007/s00415-025-13151-8.

Spatial navigation deficits in early Alzheimer's disease: the role of biomarkers and APOE genotype

Martina Laczó  1 , Zuzana Svacova  1 , Ondrej Lerch  1 , Lukas Martinkovic  1 , Monika Krejci  1   2 , Zuzana Nedelska  1 , Hana Horakova  1 , Vaclav Matoska  3 , Martin Vyhnalek  1 , Jakub Hort  1 , Michael Hornberger  4 , Jan Laczó  5
Affiliations

Spatial navigation deficits in early Alzheimer's disease: the role of biomarkers and APOE genotype

Martina Laczó et al. J Neurol. .

Abstract

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.

Keywords: Allocentric navigation; Amyloid-β; Egocentric navigation; Entorhinal cortex; Hippocampus; Tau protein.

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Conflict of interest statement

Declarations. Conflicts of interest: J.H. is a medical advisor at Neurona lab, Terrapino mobile app, consulted for Eisai, Eli Lilly, Biogen, Schwabe, and holds stock options in Alzheon. Other authors declare no competing interests. Ethical approval and consent to participate: All participants provided written informed consent according to the Declaration of Helsinki. The study was approved by the Ethics Committee of Motol University Hospital (informed consent number EK701/16).

Figures

Fig. 1
Fig. 1
Screenshots of the Virtual Supermarket Test. The video began at the start location and followed various routes to a specified end location. Participants saw the shopping trolley in front of them as they walked through the supermarket aisles
Fig. 2
Fig. 2
A spatial map of the supermarket, with the start location marked by an"X". This map shows the correct positions of all 14 end locations evaluated in the Allocentric Location Task. The trials were standardized in terms of both length and the number of turns (Section 1 lasted 20 s and included 3 turns, while Section 2 lasted 40 s and included 5 turns). Section 1, consisting of trials 1–7, was administered first, followed sequentially by Section 2, consisting of trials 8–14
Fig. 3
Fig. 3
The differences in spatial navigation performance between the groups on: a the Egocentric Heading Task, b the Allocentric Location Task, c the Allocentric Heading Task (overall performance), d the Allocentric Heading Task Section 1, and e the Allocentric Heading Task Section 2
See this image and copyright information in PMC

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