MARBLE: An in vivo MRI marker of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC).

INTRODUCTION

Limbic-predominant age-related transactive response DNA binding protein 43 kDa encephalopathy neuropathologic change (LATE-NC) is common in older adults, yet definitive diagnosis is only possible at autopsy.

METHODS

This work developed a fully automated in vivo marker of LATE-NC named MARBLE (MARker of Brain LatE) by applying machine learning methods on brain magnetic resonance imaging (MRI) and neuropathology data from 918 community-based older adults.

RESULTS

Testing MARBLE in an independent group of older adults, with ante mortem intervals between MRI and death of < 3 years, achieved an area under the curve = 0.92 for in vivo prediction of LATE-NC. Moreover, a higher MARBLE score was associated with higher LATE-NC stages (β = 0.083, 95% confidence interval = [0.053, 0.113], p < 10-4), and a lower level and accelerated decline of cognition, with the strongest effects observed in episodic and semantic memory, and perceptual speed (p < 10-4).

DISCUSSION: MARBLE is an automated in vivo MRI-based marker of LATE-NC holding significant promise for enhancing diagnosis, refining clinical trial enrollment, and advancing targeted therapeutic approaches.