Lower novelty-related locus coeruleus function is associated with Aβ-related cognitive decline in clinically healthy individuals
- PMID: 35322012
- PMCID: PMC8943159
- DOI: 10.1038/s41467-022-28986-2
Lower novelty-related locus coeruleus function is associated with Aβ-related cognitive decline in clinically healthy individuals
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.
© 2022. The Author(s).
Conflict of interest statement
K.V.P. is funded by NIA grant K23 AG053422-01 and the Alzheimer’s Association and has served as a paid consultant for Biogen. A.P.S. has been a paid consultant for Janssen, Biogen, Qynapse, and NervGen. D.M.R. has done consulting for Biogen, Idec and Digital Cognition Technologies and served on the Scientific Advisory Board for Neurotrack. R.F.B is funded by grants from the NIH K99/R00 (R00AG061238) and the Alzheimer’s Association. Y.T.Q is funded by grants from the NIH NIA (R01 AG054671, R01AG066823), the Alzheimer’s Association, and Massachusetts General Hospital ECOR, and has served as a paid consultant for Biogen. K.A.J. has served as paid consultant for Janssen, Genzyme, Novartis, Biogen, Roche, and AC Immune. He is a site co-investigator for Lilly/Avid and Janssen, and receives research support for clinical trials from Eisai, Lilly and Cerveau. K.A.J. received funding from NIH grants R01 EB014894, R21 AG038994, R01 AG026484, R01 AG034556, P50 AG00513421, U19 AG10483, P01 AG036694, R13 AG042201174210, R01 AG027435, and R01 AG037497 and the Alzheimer’s Association grant ZEN-10-174210. RAS has served as a paid consultant for AC Immune, Acumen, Alnylam, Biogen, Cytox, Genentech, Ionis, Janssen, JOMDD, Neuraly, Neurocentria, Oligomerix, Prothena, Renew, Roche, Shionogi and receives research support for clinical trials from Alzheimer’s Association, Eisai, Eli Lilly and Co. and NIA. She also receives research support from the following grant: P01 AG036694, U01 AG032438, U01 AG024904, R01 AG037497, R01 AG034556, K24 AG0350007, P50 AG005134, U19 AG010483, R01 AG027435, Fidelity Biosciences, Harvard NeuroDiscovery Center and the Alzheimer’s Association. These relationships are not related to the content in the manuscript. All other authors report no relevant conflicts.
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Comment in
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A novel link between locus coeruleus activity and amyloid-related cognitive decline.Trends Neurosci. 2022 Sep;45(9):651-653. doi: 10.1016/j.tins.2022.05.006. Epub 2022 May 31. Trends Neurosci. 2022. PMID: 35659415 Free PMC article.
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