Path integration deficits predict phosphorylated tau accumulation in the entorhinal cortex: Assessment of Braak stage I,II using 3D Virtual reality goggles

Abstract

AbstractBackgroundWe aimed to develop behavioral tasks that can identify early signs of Alzheimer’s disease (AD) in order to facilitate the development of preventative and therapeutic interventions.MethodTo do this, we created a 3D virtual reality task that is sensitive to the activity of grid cells in the entorhinal cortex, a region that is affected early on in AD. We tested path integration in a spatial navigation task in 177 volunteers between the ages of 20 and 89 who did not have a self‐diagnosed AD.ResultOur results showed that the percentage of subjects showing impaired path integration correlated with the percentage of subjects showing neurofibrillary tangles in the entorhinal cortex, as seen in previously published autopsy data. To further confirm this relationship, we also tested a tauopathy mouse model and found that mice with accumulation of phosphorylated tau in the entorhinal cortex had impaired path integration without impairments in spatial cognition or novel object recognition.ConclusionThese findings suggest that path integration deficit is caused by the accumulation of phosphorylated tau in the entorhinal cortex and may allow for early identification of individuals at risk for developing AD.