Functional Connectivity of Entorhinal Cortex Predicts Tau in the Elderly

Abstract

AbstractBackgroundHuman neuroimaging efforts to understand the pathophysiology of Alzheimer’s disease (AD) have solely focused on the amyloid‐beta (Aβ) deposition and tau neurofibrillary tangle formation. Until recently, the idea of a connectivity‐based molecular functional framework for understanding AD pathophysiology was missing, which eluded researchers from connecting functional connectivity (FC) with Aβ/Tau deposition.MethodThe initial dataset includes 631 older (67.44 ± 6.48 years) adults (521 healthy controls and 110 mild cognitive impairment (MCI)) who have been imaged for Tau pathology as well as resting‐state functional magnetic resonance imaging (rsfMRI) and structural MRI scans. Using Schaefer’s 200 parcellation atlas and a regional cutoff (SUVR = 1.25), we identified four groups of tau staging based on the number of regions having higher than cutoff tau SUVR (no tau stage (N = 193), pre‐acceleration stage (N = 222), acceleration stage (N = 149), and post‐acceleration stage (N = 67)). Since the entorhinal cortex (EC) is widely regarded as the epi‐center for tau accumulation, the left and right EC time series were derived from rsfMRI data using the Desikan‐Killiany atlas and used as seed regions for our Pearson correlation coefficient based functional connectivity analysis with all 200 regions in the Schaefer atlas. Finally, linear regression models were run to predict the mean regional accumulation of tau based on the strength of mean FC between that region and EC.ResultAs shown in Fig. 1, left/right EC functional connectivity is strongly associated with the accumulation of tau in that region during the pre‐acceleration phase (left: t = 3.586, p < 0.0004; right: t = 4.404, p < 0.0001) and in the acceleration phase (left: t = 6.229, p < 0.0001; right: t = 7.577, p < 0.0001) (results not shown). The functional connectivity values from left/right EC for the pre‐acceleration phase are plotted on the surface of the brain, as shown in Fig. 2.ConclusionOur results provide evidence of the role of functional connectivity in tau spreading from EC to the rest of the brain and can help throw light on the dynamic patterns of tau spreading in MCI/AD subjects in different disease stages.