Lower novelty-related locus coeruleus function is associated with Aβ-related cognitive decline in clinically healthy individuals

Prokopis C. Prokopiou, Nina Engels-Domínguez, Kathryn V. Papp, Matthew R. Scott, Aaron P. Schultz, Christoph Schneider, Michelle E. Farrell, Rachel F. Buckley, Yakeel T. Quiroz, Georges El Fakhri, Dorene M. Rentz, Reisa A. Sperling, Keith A. Johnson and Heidi I. L. Jacobs ()
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Prokopis C. Prokopiou: Massachusetts General Hospital, Harvard Medical School
Nina Engels-Domínguez: Massachusetts General Hospital, Harvard Medical School
Kathryn V. Papp: Brigham and Women’s Hospital, Harvard Medical School
Matthew R. Scott: Massachusetts General Hospital, Harvard Medical School
Aaron P. Schultz: Massachusetts General Hospital, Harvard Medical School
Christoph Schneider: Massachusetts General Hospital, Harvard Medical School
Michelle E. Farrell: Massachusetts General Hospital, Harvard Medical School
Rachel F. Buckley: Brigham and Women’s Hospital, Harvard Medical School
Yakeel T. Quiroz: Massachusetts General Hospital, Harvard Medical School
Georges El Fakhri: Massachusetts General Hospital, Harvard Medical School
Dorene M. Rentz: Brigham and Women’s Hospital, Harvard Medical School
Reisa A. Sperling: Brigham and Women’s Hospital, Harvard Medical School
Keith A. Johnson: Massachusetts General Hospital, Harvard Medical School
Heidi I. L. Jacobs: Massachusetts General Hospital, Harvard Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Animal and human imaging research reported that the presence of cortical Alzheimer’s Disease’s (AD) neuropathology, beta-amyloid and neurofibrillary tau, is associated with altered neuronal activity and circuitry failure, together facilitating clinical progression. The locus coeruleus (LC), one of the initial subcortical regions harboring pretangle hyperphosphorylated tau, has widespread connections to the cortex modulating cognition. Here we investigate whether LC’s in-vivo neuronal activity and functional connectivity (FC) are associated with cognitive decline in conjunction with beta-amyloid. We combined functional MRI of a novel versus repeated face-name paradigm, beta-amyloid-PET and longitudinal cognitive data of 128 cognitively unimpaired older individuals. We show that LC activity and LC-FC with amygdala and hippocampus was higher during novelty. We also demonstrated that lower novelty-related LC activity and LC-FC with hippocampus and parahippocampus were associated with steeper beta-amyloid-related cognitive decline. Our results demonstrate the potential of LC’s functional properties as a gauge to identify individuals at-risk for AD-related cognitive decline.

Date: 2022
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DOI: 10.1038/s41467-022-28986-2

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