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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-05-2019 | Alzheimer's Disease | Original Article

Longitudinal tau and metabolic PET imaging in relation to novel CSF tau measures in Alzheimer’s disease

Authors: Antoine Leuzy, Claudia Cicognola, Konstantinos Chiotis, Laure Saint-Aubert, Laetitia Lemoine, Niels Andreasen, Henrik Zetterberg, Keqiang Ye, Kaj Blennow, Kina Höglund, Agneta Nordberg

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 5/2019

Abstract

Purpose

Studies comparing CSF and PET tau biomarkers have included only commercial CSF assays examining specific phosphorylation sites (e.g. threonine 181, P-tau_181p) 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-tau_181p 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-tau_181p and T-tau, tau-368 and tau N-Mid may better capture tau pathology and synaptic impairment.

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Title: Longitudinal tau and metabolic PET imaging in relation to novel CSF tau measures in Alzheimer’s disease
Authors: Antoine Leuzy
Claudia Cicognola
Konstantinos Chiotis
Laure Saint-Aubert
Laetitia Lemoine
Niels Andreasen
Henrik Zetterberg
Keqiang Ye
Kaj Blennow
Kina Höglund
Agneta Nordberg
Publication date: 01-05-2019
Publisher: Springer Berlin Heidelberg
Keywords: Alzheimer's Disease
Dementia
Positron Emission Tomography
Alzheimer's Disease
Dementia
Biomarkers
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 5/2019
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-018-4242-6

At a glance: The STEP trials

Springer Medicine

Longitudinal tau and metabolic PET imaging in relation to novel CSF tau measures in Alzheimer’s disease

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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