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

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.

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.

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).

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.