Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition

Elisenda Bueichekú; Ibai Diez; Chan-Mi Kim; John Alex Becker; Elouise A Koops; Kenneth Kwong; Kathryn V Papp; David H Salat; David A Bennett; Dorene M Rentz; Reisa A Sperling; Keith A Johnson; Jorge Sepulcre; Heidi I L Jacobs

doi:10.1038/s43587-024-00626-y

Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition

Nat Aging. 2024 Apr 25. doi: 10.1038/s43587-024-00626-y. Online ahead of print.

Authors

Elisenda Bueichekú^{1

2}, Ibai Diez^{1

2

3}, Chan-Mi Kim^{1

2}, John Alex Becker^{1

2}, Elouise A Koops², Kenneth Kwong^{2

3}, Kathryn V Papp^{2

4

5}, David H Salat^{2

3

6}, David A Bennett^{7

8}, Dorene M Rentz^{2

4

5}, Reisa A Sperling^{2

4

5}, Keith A Johnson^{1

2

5}, Jorge Sepulcre^#^{9

10

11

12}, Heidi I L Jacobs^#^{13

14

15}

Affiliations

¹ Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
² Harvard Medical School, Boston, MA, USA.
³ The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
⁴ Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
⁵ Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
⁶ Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA.
⁷ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
⁸ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
⁹ Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA. jorge.sepulcre@yale.edu.
¹⁰ Harvard Medical School, Boston, MA, USA. jorge.sepulcre@yale.edu.
¹¹ The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA. jorge.sepulcre@yale.edu.
¹² Department of Radiology, Yale PET Center, Yale Medical School, Yale University, New Haven, CT, USA. jorge.sepulcre@yale.edu.
¹³ Harvard Medical School, Boston, MA, USA. hjacobs@mgh.harvard.edu.
¹⁴ The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA. hjacobs@mgh.harvard.edu.
¹⁵ Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, Netherlands. hjacobs@mgh.harvard.edu.

^# Contributed equally.

PMID: 38664576
DOI: 10.1038/s43587-024-00626-y

Abstract

Autopsy studies indicated that the locus coeruleus (LC) accumulates hyperphosphorylated tau before allocortical regions in Alzheimer's disease. By combining in vivo longitudinal magnetic resonance imaging measures of LC integrity, tau positron emission tomography imaging and cognition with autopsy data and transcriptomic information, we examined whether LC changes precede allocortical tau deposition and whether specific genetic features underlie LC's selective vulnerability to tau. We found that LC integrity changes preceded medial temporal lobe tau accumulation, and together these processes were associated with lower cognitive performance. Common gene expression profiles between LC-medial temporal lobe-limbic regions map to biological functions in protein transport regulation. These findings advance our understanding of the spatiotemporal patterns of initial tau spreading from the LC and LC's selective vulnerability to Alzheimer's disease pathology. LC integrity measures can be a promising indicator for identifying the time window when individuals are at risk of disease progression and underscore the importance of interventions mitigating initial tau spread.

Abstract

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