EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING

Leuzy A, Cicognola C, Chiotis K, Saint-Aubert L, Lemoine L, Andreasen N, Zetterberg H, Ye K, Blennow K, Hoglund K and Nordberg A

Eur J Nucl Med Mol Imaging. 2019 Jan 4

DOI: 10.1007/s00259-018-4242-6

This study was peformed using a Simoa® Homebrew assay.

Abstract

Purpose:

Studies comparing CSF and PET tau biomarkers have included only commercial CSF assays examining specific phosphorylation sites (e.g. threonine 181, P-tau181p) and mid-domain tau (i.e. total tau, T-tau). Moreover, these studies did not examine CSF tau levels in relation to cerebral glucose metabolism. We thus aimed to examine CSF tau measures, using both commercial and novel assays, in relationto [18F]THK5317 (tau) and [18F]FDG PET (glucose metabolism).

Methods:

Fourteen Alzheimer’s disease (AD) patients (seven prodromal, seven dementia) underwent [18F]THK5317 and [18F]FDG PETstudies, with follow-up performed in ten subjects (six prodromal, four dementia) after 17 months. In addition to commercial assays, novelmeasures capturing N-terminus+mid-domain (tau N-Mid) and C-terminally truncated (tau-368) fragments were included.

Results:

While the levels of all forms of CSF tau were found to be inversely associated with baseline [18F]FDG uptake, associations with baseline [18F]THK5317 uptake varied in relation to the degree of isocortical hypometabolism ([18F]FDG SUVR). Changes in the levels of the novel CSF markers tracked longitudinal changes in tracer uptake better than changes in P-tau181p and T-tau levels, and improved concordance with dichotomized regional [18F]THK5317 measures.

Conclusion:

Our findings suggest that neurodegeneration may modulate the relationship between CSF and PET tau biomarkers, and that, by comparison to P-tau181p and T-tau, tau-368 and tau N-Mid may better capture tau pathology and synaptic impairment.