Structural compression and entorhinal vulnerability: Linking tentorial adjacency to tau burden and dementia progression

Abstract

INTRODUCTION

Early neurofibrillary tau degeneration in the entorhinal cortex (EC) is a hallmark of Alzheimer's disease (AD) and aging. We propose a biomechanical cascade hypothesis, suggesting proximity to the tentorial incisura (TI) may render the EC susceptible to chronic mechanical stress, potentially contributing to tau pathology.

METHODS

We developed a neuroanatomical contact coefficient (NCC) to quantify EC–TI proximity using Alzheimer's Disease Neuroimaging Initiative multimodal imaging data (n = 47), stratifying participants into high and low adjacency groups.

RESULTS

Controlling for risk factors, EC tau positron emission tomography signal predicted conversion from mild cognitive impairment to AD only in the high-adjacency group (P = 0.036).

DISCUSSION

Findings identify EC–TI proximity as a potential, novel, anatomically grounded biomarker of AD risk. These findings are consistent with a previously unrecognized biomechanical contribution to EC tau vulnerability in sporadic AD and aging, opening new avenues for early detection, risk stratification, and mechanistically targeted prevention strategies.