Journal Article Epublish 2 citations
PubMed: 40016783 DOI: 10.1186/s13195-025-01701-1
Probing locus coeruleus functional network in healthy aging and its association with Alzheimer's disease biomarkers using pupillometry.
Alzheimers Res Ther 17(1):53
Authors: Junjie Wu, Aaron Toporek, Qixiang Lin, Felicia C Goldstein, David W Loring, Michael A Kelberman, David Weinshenker, Allan I Levey, James J Lah, Deqiang Qiu
Affiliations
- Department of Radiology and Imaging Sciences, School of Medicine, Emory University, 1364 Clifton Rd NE, Atlanta, GA, 30322, USA.
- Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA.
- Department of Radiology and Imaging Sciences, School of Medicine, Emory University, 1364 Clifton Rd NE, Atlanta, GA, 30322, USA. School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
- Goizueta Alzheimer's Disease Research Center, Emory University, Atlanta, GA, USA.
- Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA.
- Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, USA.
- Department of Radiology and Imaging Sciences, School of Medicine, Emory University, 1364 Clifton Rd NE, Atlanta, GA, 30322, USA.
- Goizueta Alzheimer's Disease Research Center, Emory University, Atlanta, GA, USA.
- Joint Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
Abstract
BACKGROUND
Alzheimer's disease (AD) is the leading cause of dementia, and the early detection of the disease-associated changes allows early interventions. The locus coeruleus (LC) has been reported to be the first brain region to develop tau pathology in AD. However, the functional brain network of the LC in both healthy aging and AD pathology is largely unknown due to technical difficulties associated with the small size of the LC. In this study, we used the measurement of spontaneous pupil constriction/dilation as a surrogate for LC activity to study LC brain network changes during healthy aging.
METHODS
Thirty-seven healthy younger and thirty-nine healthy older adults were included from the Emory Healthy Brain Study and underwent resting-state functional MRI while simultaneously tracking pupil diameter. The measurements of pupil diameter dynamics were used as reference signals in brain connectivity analysis. The connectivity of the identified networks was then compared between younger and older participants. Correlations of the identified regions with neuropsychological assessments and cerebrospinal fluid (CSF) biomarkers were also evaluated.
RESULTS
A brain network of 20 clusters associated with pupil diameter dynamics was identified, including the LC as well as brain regions functionally connected to the LC. The pupil diameter network was found to positively correlate with the salience network and negatively correlate with the central executive network. Functional connectivity decreased within the pupil diameter network with healthy aging. The pupil diameter connectivity was associated with memory, executive, and visuospatial functioning. CSF total tau closely correlated with pupil diameter network.
CONCLUSIONS
Pupil diameter dynamics provide valuable insights into LC-related processes. While they are not solely influenced by LC activity, spontaneous pupil constrictor/dilatory activity shows promise as a non-invasive approach to probe the LC network and warrants further studies to evaluate its value as an early biomarker of AD.
MeSH
Research Design, Locus Coeruleus, Alzheimer Disease, Aging, Brain, Pupil, Pathology, Biomarkers, Healthy Aging