Locus coeruleus MRI contrast, cerebral perfusion, and plasma Alzheimer's disease biomarkers in older adults

Shubir Dutt¹, Shelby L Bachman², Martin J Dahl³, Yanrong Li⁴, Belinda Yew⁵, Jung Yun Jang⁴, Jean K Ho⁴, Kaoru Nashiro², Jungwon Min², Hyun Joo Yoo², Aimée Gaubert², Amy Nguyen², Anna E Blanken⁶, Isabel J Sible⁷, Anisa J Marshall⁷, Arunima Kapoor⁸, John Paul M Alitin², Kim Hoang⁴, Jeremy Rouanet⁹, Lorena Sordo⁹, Elizabeth Head⁹, Xingfeng Shao¹⁰, Danny J J Wang¹⁰, Mara Mather², Daniel A Nation¹¹

Affiliations

¹ Department of Psychology, University of Southern California, Los Angeles, CA, USA; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.
² Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
³ Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA; Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
⁴ Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
⁵ Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA; San Francisco Veterans Affairs Health Care System, CA, USA.
⁷ Department of Psychology, University of Southern California, Los Angeles, CA, USA.
⁸ Department of Psychological Science, University of California, Irvine, CA, USA.
⁹ Department of Pathology & Laboratory Medicine, University of California, Irvine, CA, USA.
¹⁰ Laboratory of FMRI Technology, Mark & Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, CA, Los Angeles, USA.
¹¹ Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA; Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, CA, Los Angeles, USA. Electronic address: danation@usc.edu.

PMID: 39637519
PMCID: PMC11781958 (available on 2026-03-01)
DOI: 10.1016/j.neurobiolaging.2024.11.008

Locus coeruleus MRI contrast, cerebral perfusion, and plasma Alzheimer's disease biomarkers in older adults

Shubir Dutt et al. Neurobiol Aging. 2025 Mar.

. 2025 Mar:147:12-21.

doi: 10.1016/j.neurobiolaging.2024.11.008. Epub 2024 Nov 27.

Authors

Affiliations

¹ Department of Psychology, University of Southern California, Los Angeles, CA, USA; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.
² Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
³ Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA; Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
⁴ Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
⁵ Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA; San Francisco Veterans Affairs Health Care System, CA, USA.
⁷ Department of Psychology, University of Southern California, Los Angeles, CA, USA.
⁸ Department of Psychological Science, University of California, Irvine, CA, USA.
⁹ Department of Pathology & Laboratory Medicine, University of California, Irvine, CA, USA.
¹⁰ Laboratory of FMRI Technology, Mark & Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, CA, Los Angeles, USA.
¹¹ Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA; Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, CA, Los Angeles, USA. Electronic address: danation@usc.edu.

PMID: 39637519
PMCID: PMC11781958 (available on 2026-03-01)
DOI: 10.1016/j.neurobiolaging.2024.11.008

Abstract

The locus coeruleus (LC) is among the first brain structures impacted by Alzheimer's disease (AD), and noradrenergic denervation may contribute to early neurovascular dysfunction in AD. Mechanistic links between the LC and cerebral perfusion have been demonstrated in rodents, but there have been no similar studies in aging humans. Community-dwelling older adults with no history of stroke or dementia (N=66) underwent structural (T1-MPRAGE; T1-FSE) and perfusion (resting pCASL) MRI. Plasma AD biomarkers levels were evaluated for Aβ42/40 ratio (n=56) and pTau181 (n=60). Higher rostral LC structural MRI contrast was associated with lower perfusion in entorhinal and limbic regions but higher perfusion in lateral and medial orbitofrontal cortices. Relationships between LC structure and regional cerebral perfusion were attenuated in older adults with higher plasma pTau levels and lower plasma Aβ42/40 ratios. Previously unstudied links between LC structure and cerebral perfusion are detectible in older adults using MRI and are attenuated in those showing greater AD pathophysiologic change, suggesting an uncoupling of LC-cerebral perfusion relationships in older adults with aggregating AD-related pathophysiology.

Keywords: Alzheimer’s disease; cerebral blood flow; locus coeruleus; older adults; plasma biomarkers.

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Conflict of interest statement

Disclosure statement The authors confirm that no conflicts of interest exist.

References

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Locus coeruleus MRI contrast, cerebral perfusion, and plasma Alzheimer's disease biomarkers in older adults

Affiliations

Locus coeruleus MRI contrast, cerebral perfusion, and plasma Alzheimer's disease biomarkers in older adults

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical