AD_GRIDS - altered grid cell computations in entorhinal cortex as a unique window into preclinical Alzheimer’s disease?

Thomas Wolbers (Germany), Mallar Chakravarty (Canada)

Spatial navigation is a fundamental cognitive ability that is often impaired in advanced stages of Alzheimer’s disease (AD). One central component of the brain’s navigational system is the grid cell network in entorhinal cortex, whose discovery was awarded the Nobel Prize for Medicine/Physiology in 2014. Given that entorhinal cortex is particularly vulnerable to neurodegenerative changes in the earliest stages of AD, deficits in grid cell function could provide a unique functional window into early AD pathology. This project will break new ground by investigating (i) the mechanisms that compromise the integrity of the grid cell network in mouse models of AD pathology and in patients with Subjective Cognitive Decline, and (ii) whether a behavioral readout of grid cell functioning can improve the detection of preclinical disease stages. To address these important questions, the team will employ an interdisciplinary methodological approach that combines advanced behavioral and neuroscientific approaches with innovative data analysis techniques. Moreover, we will employ cutting-edge user-interface design principles to establish a standardised test of grid cell functioning that fulfills the requirements of clinical settings. Together, AD_GRIDS has the potential to significantly advance the detection of early disease stages, the monitoring of disease progression and the assessment of treatment efficacy.

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