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Peer-reviewedCC BY-NC-ND 4.0Alzheimer's & Dementia

Locus coeruleus microstructural integrity and sleep disruption in the context of Alzheimer's disease pathology

  • Maxime Van Egroo1,2
  • Yuliya Patsyuk1
  • Marion Baillet2
  • Nicholas M. Vogt2,3
  • Andrew S. P. Lim4
  • Nicholas J. Ashton5,6,7
  • Shorena Janelidze8
  • Kaj Blennow5,9
  • Oskar Hansson8
  • Henrik Zetterberg5,10,11,12,13,14,15
  • Heidi I. L. Jacobs1,2
15 affiliations
  1. 1Faculty of Health, Medicine and Life Sciences, Mental Health and Neuroscience Research Institute, Alzheimer Centre Limburg Maastricht University Maastricht the Netherlands
  2. 2Athinoula A. Martinos Center for Biomedical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston Massachusetts USA
  3. 3Hinda and Arthur Marcus Institute for Aging Research Hebrew SeniorLife Boston Massachusetts USA
  4. 4Department of Neurology University of Toronto Toronto Ontario Canada
  5. 5Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, The Sahlgrenska Academy, The University of Gothenburg Mölndal Sweden
  6. 6Banner Alzheimer's Institute and University of Arizona Phoenix Arizona USA
  7. 7Banner Sun Health Research Institute Sun City Arizona USA
  8. 8Clinical Memory Research Unit Department of Clinical Sciences Malmö Lund University Lund Sweden
  9. 9Eli Lilly and Company Gothenburg Sweden
  10. 10Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden
  11. 11Department of Neurodegenerative Disease UCL Institute of Neurology, Queen Square London UK
  12. 12UK Dementia Research Institute at UCL London UK
  13. 13Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay Hong Kong China
  14. 14Department of Pathology and Laboratory Medicine University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA
  15. 15Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health University of Wisconsin–Madison Madison Wisconsin USA
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{egroo2026locus,
  title = {{Locus coeruleus microstructural integrity and sleep disruption in the context of Alzheimer's disease pathology}},
  author = {Maxime Van Egroo and Yuliya Patsyuk and Marion Baillet and Nicholas M. Vogt and Andrew S. P. Lim and Nicholas J. Ashton and Shorena Janelidze and Kaj Blennow and Oskar Hansson and Henrik Zetterberg and Heidi I. L. Jacobs},
  journal = {Alzheimer's \& Dementia},
  year = {2026},
  month = nov,
  doi = {10.1002/alz.71964},
  url = {https://doi.org/10.1002/alz.71964},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Locus coeruleus microstructural integrity and sleep disruption in the context of Alzheimer's disease pathology
AU  - Maxime Van Egroo
AU  - Yuliya Patsyuk
AU  - Marion Baillet
AU  - Nicholas M. Vogt
AU  - Andrew S. P. Lim
AU  - Nicholas J. Ashton
AU  - Shorena Janelidze
AU  - Kaj Blennow
AU  - Oskar Hansson
AU  - Henrik Zetterberg
AU  - Heidi I. L. Jacobs
PY  - 2026
DA  - 2026/11/04
JO  - Alzheimer's & Dementia
DO  - 10.1002/alz.71964
UR  - https://doi.org/10.1002/alz.71964
AB  - 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.
SN  - 1552-5260
SN  - 1552-5279
ER  -