Ontology highlight
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 relation to [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 PET studies, with follow-up performed in ten subjects (six prodromal, four dementia) after 17 months. In addition to commercial assays, novel measures 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.
SUBMITTER: Leuzy A
PROVIDER: S-EPMC6451715 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
Leuzy Antoine A Cicognola Claudia C Chiotis Konstantinos K Saint-Aubert Laure L Lemoine Laetitia L Andreasen Niels N Zetterberg Henrik H Ye Keqiang K Blennow Kaj K Höglund Kina K Nordberg Agneta A
European journal of nuclear medicine and molecular imaging 20190104 5
<h4>Purpose</h4>Studies comparing CSF and PET tau biomarkers have included only commercial CSF assays examining specific phosphorylation sites (e.g. threonine 181, P-tau<sub>181p</sub>) 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 relation to [<sup>18</sup>F]THK5317 (tau) and [<sup>18</sup>F]FDG PET (glucose metabo ...[more]