Cohort study of electroencephalography markers of amyloid-tau-neurodegeneration pathology

Sean Tanabe; Amber Bo; Marissa White; Margaret Parker; Zahra Farahbakhsh; Tyler Ballweg; Cameron Casey; Tobey Betthauser; Henrik Zetterberg; Kaj Blennow; Brad Christian; Barbara B Bendlin; Sterling Johnson; Robert D Sanders

doi:10.1093/braincomms/fcaa099

Cohort study of electroencephalography markers of amyloid-tau-neurodegeneration pathology

Brain Commun. 2020 Jul 15;2(2):fcaa099. doi: 10.1093/braincomms/fcaa099. eCollection 2020.

Authors

Sean Tanabe¹, Amber Bo¹, Marissa White¹, Margaret Parker¹, Zahra Farahbakhsh¹, Tyler Ballweg¹, Cameron Casey¹, Tobey Betthauser², Henrik Zetterberg^{3

4

5

6}, Kaj Blennow^{3

4}, Brad Christian⁷, Barbara B Bendlin², Sterling Johnson², Robert D Sanders^{8

9}

Affiliations

¹ Department of Anesthesiology, University of Wisconsin, Madison, WI, USA.
² Department of Medicine, Division of Geriatrics, University of Wisconsin, Madison, WI, USA.
³ Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁴ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁵ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
⁶ UK Dementia Research Institute at UCL, London, UK.
⁷ Department of Medical Physics and Psychiatry, University of Wisconsin, Madison, WI, USA.
⁸ Discipline of Anaesthetics, University of Sydney, Sydney, Australia.
⁹ Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

Abstract

Electroencephalography signatures of amyloid-β, tau and neurodegenerative pathologies would aid in screening for, tracking progression of, and critically, understanding the pathogenesis of dementia. We hypothesized that slowing of the alpha peak frequency, as a signature of hyperpolarization-activated cyclic nucleotide gated 'pacemaker' channel activity, would correlate with amyloid and tau pathology burden measured by amyloid (Pittsburgh Compound B) and tau (MK-6240) positron emission tomography or CSF biomarkers. We also hypothesized that EEG power would be associated with neurodegeneration (CSF neurofilament light and hippocampal volume). Wakeful high-density EEG data were collected from 53 subjects. Both amyloid-β and tau pathology were associated with slowing in the alpha peak frequency [Pittsburgh Compound B (+) vs. Pittsburgh Compound B (-) subjects, P = 0.039 and MK-6240 (+) vs. MK-6240 (-) subjects, P = 0.019]. Furthermore, slowing in the peak alpha frequency correlated with CSF Aβ_42/40 ratio (r ² = 0.270; P = 0.003), phosphoTau (pTau₁₈₁, r ² = 0.290; P = 0.001) and pTau₁₈₁/Aβ₄₂ (r ² = 0.343; P < 0.001). Alpha peak frequency was not associated with neurodegeneration. Higher CSF neurofilament light was associated with lower total EEG power (r ² = 0.136; P = 0.018), theta power (r ² = 0.148; P = 0.014) and beta power (r ² = 0.216; P = 0.002); the latter was also associated with normalized hippocampal volume (r ² = 0.196; P = 0.002). Amyloid-tau and neurodegenerative pathologies are associated with distinct electrophysiological signatures that may be useful as mechanistic tools and diagnostic/treatment effect biomarkers in clinical trials.

Keywords: EEG; alpha; amyloid; neurodegeneration; tau.

Abstract

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