Vulnerability of locus coeruleus connections to aging and Alzheimer's disease.

INTRODUCTION

The locus coeruleus (LC) is important in coordinating communication between brain regions through its widespread connections. However, the organization of its connections, and its changes with aging and Alzheimer's disease (AD), remains unclear.

METHODS

We mapped whole-brain white matter connections from the LC in two independent cohorts: one spanning the adult lifespan and another covering the AD continuum.

RESULTS

We identified a novel dorsal-ventral organization of LC connectivity that showed changes common to aging and AD or specific to AD, was linked to gene expression patterns, and was associated with cognitive performance and tau pathology in the entorhinal cortex. We also developed an imaging marker, LC gap, capturing LC connectivity deviations associated with slower tau accumulation in cognitively normal individuals at high risk for AD.

DISCUSSION: These findings provide new insights into LC connectivity in aging and AD, highlighting its potential role as a resilience marker against AD neurodegeneration.