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Brainstem tau protein burden is associated with cortical hyper‐excitability in healthy aging
Author(s) -
Van Egroo Maxime
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.038068
Subject(s) - brainstem , neuroscience , monoaminergic , locus coeruleus , thalamus , white matter , psychology , medicine , magnetic resonance imaging , central nervous system , receptor , serotonin , radiology
Background Alzheimer’s disease (AD) neuropathology spreads over decades prior to cognitive symptom onset. Its first signs consist in misfolded tau protein accumulation in the brainstem, particularly in the locus coeruleus (LC). Neuronal hyper‐excitability also occurs early in the pathogenesis of AD and contributes to neuronal network dysfunction. Here, we tested whether early cortical hyper‐excitability may be related to tau aggregates in the brainstem. Method We probed cortical excitability over the frontal cortex using transcranial magnetic stimulation combined with electroencephalography in a sample of late middle‐aged healthy individuals (n = 65; 50‐70 years). We assessed whole‐brain tau protein burden with [18F] THK5351 positron emission tomography and we extracted radiotracer uptake values in a brainstem monoaminergic compartment including notably the LC. Diffusion‐weighted magnetic resonance imaging data were also acquired to explore cortico‐LC white matter pathways. Result We found that higher tau burden in the brainstem monoaminergic grey matter was specifically associated with increased cortical excitability. By contrast, tau deposits in the hippocampus and entorhinal cortex, although correlating with brainstem tau signal, were not associated with cortical excitability. Tractography analysis revealed that frontal cortical excitability was linked to the integrity of the tracts connecting the frontal cortex and a dorsal pontine tegmentum area encompassing the LC. Conclusion These findings reveal potential brain substrates for increased cortical excitability in preclinical and early AD, and they constitute the first human functional correlates of in vivo early tau protein accumulation in the brainstem.