Graichen, L. P. | bioRxiv Science

bioRxiv2026

No effects of APOE ε4 on spatial navigation and broader cognition in young adults genetically at risk for Alzheimer's disease

Alzheimers disease (AD) causes progressive memory loss and disorientation. It is preceded by a prolonged preclinical phase marked by pathological changes in medial temporal lobe regions involved in spatial navigation. Spatial navigation tasks have been proposed for early AD detection, and altered navigation performance was reported in older carriers of the apolipoprotein E (APOE) {varepsilon}4 allele, the major genetic risk factor for sporadic AD. However, whether spatial navigation or other cognitive abilities are affected in younger {varepsilon}4 carriers remains unclear. Here, we genotyped 1000 healthy young adults (18-35 years) who completed the app-based navigation game "Sea Hero Quest" and several tasks assessing working memory, processing speed, executive functioning, and face recognition. {varepsilon}4 carriers ({varepsilon}3{varepsilon}4, N = 88) showed no significant differences from non-carriers ({varepsilon}3{varepsilon}3, N = 327) in spatial navigation or other cognitive abilities, supported by equivalence testing and Bayesian analyses. Exploratory findings suggested altered spatial navigation in {varepsilon}2 carriers ({varepsilon}2{varepsilon}2/{varepsilon}2{varepsilon}3/{varepsilon}2{varepsilon}4, Ns = 7/51/7) versus {varepsilon}3{varepsilon}3 controls, who stayed closer to environmental borders and showed better memory updating, face recognition, and processing speed. Therefore, APOE-related behavioural differences in young adults appear small at best, highlighting the need for paradigms sensitive to very subtle changes decades before potential dementia onset.

neuroscience↗

bioRxiv2024

Entorhinal grid-like codes for visual space during memory formation

Eye movements, such as saccades, allow us to gather information about the environment and, in this way, can shape memory. In non-human primates, saccades are associated with the activity of grid cells in the entorhinal cortex. Grid cells are essential for spatial navigation, but whether saccade-based grid-like signals play a role in human memory formation is currently unclear. Here, human participants underwent functional magnetic resonance imaging (fMRI) and continuous eye gaze monitoring while studying scene images. Recognition memory was probed immediately thereafter. Results revealed saccade-based grid-like codes in the left entorhinal cortex while participants studied the scene images, a finding that was replicated with an independent data set reported here. The grid-related effects were time-locked to activation increases in the frontal eye fields. Most importantly, saccade-based grid-like codes were associated with recognition memory, such that grid-like codes were lower the better participants performed in subsequently recognizing the scene images. Collectively, our findings suggest an entorhinal map of visual space that is timed with neural activity in oculomotor regions, supporting memory formation.

neuroscience↗