Locus coeruleus microstructural integrity and sleep disruption in the context of Alzheimer's disease pathology
Maxime Van Egroo, Yuliya Patsyuk, Marion Baillet, Nicholas M. Vogt, Andrew S. P. Lim, Nicholas J. Ashton, Shorena Janelidze, Kaj Blennow, Oskar Hansson, Henrik Zetterberg, Heidi I. L. JacobsAbstract
INTRODUCTION
The locus coeruleus (LC) is among the first sites of tau pathology in Alzheimer's disease (AD) and plays a key role in sleep–wake regulation. However, evidence linking LC integrity to objective sleep measures in the context of emerging AD pathology remains limited.
METHODS
Thirty‐nine cognitively unimpaired older adults underwent dedicated LC and neurite orientation dispersion and density imaging at 7T magnetic resonance imaging, actigraphy, and quantification of plasma AD‐related biomarkers. A subsample of 20 individuals also completed at‐home sleep electroencephalogram (EEG) recordings.
RESULTS
Lower LC orientation dispersion index, indicating lower complexity in the arborization of LC neurites, was associated with actigraphy‐ and EEG‐derived measures of shorter and more fragmented sleep. These associations were exacerbated at elevated plasma phosphorylated tau 217 and glial fibrillary acidic protein concentrations.
DISCUSSION
Our findings provide in vivo evidence of the LC's involvement in sleep disruption, and they highlight LC microstructure as a potential marker for identifying individuals at risk for AD‐related sleep disturbances.