Longitudinal tau and metabolic PET imaging in relation to novel CSF tau measures in Alzheimer’s disease
Leuzy, Antoine LU ; Cicognola, Claudia LU
; Chiotis, Konstantinos
; Saint-Aubert, Laure
; Lemoine, Laetitia
; Andreasen, Niels
; Zetterberg, Henrik
LU
; Ye, Keqiang
; Blennow, Kaj
LU
and Höglund, Kina
, et al.
(2019)
In European Journal of Nuclear Medicine and Molecular Imaging
46(5).
p.1152-1163
- 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 [ 18 F]THK5317 (tau) and [ 18 F]FDG PET (glucose metabolism). Methods: Fourteen Alzheimer’s disease (AD)... (More)
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 [ 18 F]THK5317 (tau) and [ 18 F]FDG PET (glucose metabolism). Methods: Fourteen Alzheimer’s disease (AD) patients (seven prodromal, seven dementia) underwent [ 18 F]THK5317 and [ 18 F]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 [ 18 F]FDG uptake, associations with baseline [ 18 F]THK5317 uptake varied in relation to the degree of isocortical hypometabolism ([ 18 F]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 [ 18 F]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.
(Less)
- author
- Leuzy, Antoine
LU
; Cicognola, Claudia
LU
; Chiotis, Konstantinos
; Saint-Aubert, Laure
; Lemoine, Laetitia
; Andreasen, Niels
; Zetterberg, Henrik
LU
; Ye, Keqiang
; Blennow, Kaj
LU
and Höglund, Kina
, et al. (More)
- Leuzy, Antoine
LU
; Cicognola, Claudia
LU
; Chiotis, Konstantinos
; Saint-Aubert, Laure
; Lemoine, Laetitia
; Andreasen, Niels
; Zetterberg, Henrik
LU
; Ye, Keqiang
; Blennow, Kaj
LU
; Höglund, Kina
and Nordberg, Agneta
(Less)
- publishing date
- 2019-05-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer’s disease, CSF, PET imaging, Tau, [ F]FDG, [ F]THK5317
- in
- European Journal of Nuclear Medicine and Molecular Imaging
- volume
- 46
- issue
- 5
- pages
- 12 pages
- publisher
- Springer
- external identifiers
-
- pmid:30610252
- scopus:85059651010
- ISSN
- 1619-7070
- DOI
- 10.1007/s00259-018-4242-6
- language
- English
- LU publication?
- no
- id
- 24f2f050-8cc9-4791-81d7-fe43e9975da5
- date added to LUP
- 2020-02-25 09:49:58
- date last changed
- 2024-10-02 21:53:23
@article{24f2f050-8cc9-4791-81d7-fe43e9975da5,
abstract = {{<p> Purpose: 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 metabolism). Methods: Fourteen Alzheimer’s disease (AD) patients (seven prodromal, seven dementia) underwent [ <sup>18</sup> F]THK5317 and [ <sup>18</sup> F]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 [ <sup>18</sup> F]FDG uptake, associations with baseline [ <sup>18</sup> F]THK5317 uptake varied in relation to the degree of isocortical hypometabolism ([ <sup>18</sup> F]FDG SUVR). Changes in the levels of the novel CSF markers tracked longitudinal changes in tracer uptake better than changes in P-tau <sub>181p</sub> and T-tau levels, and improved concordance with dichotomized regional [ <sup>18</sup> F]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 <sub>181p</sub> and T-tau, tau-368 and tau N-Mid may better capture tau pathology and synaptic impairment. </p>}},
author = {{Leuzy, Antoine and Cicognola, Claudia and Chiotis, Konstantinos and Saint-Aubert, Laure and Lemoine, Laetitia and Andreasen, Niels and Zetterberg, Henrik and Ye, Keqiang and Blennow, Kaj and Höglund, Kina and Nordberg, Agneta}},
issn = {{1619-7070}},
keywords = {{Alzheimer’s disease; CSF; PET imaging; Tau; [ F]FDG; [ F]THK5317}},
language = {{eng}},
month = {{05}},
number = {{5}},
pages = {{1152--1163}},
publisher = {{Springer}},
series = {{European Journal of Nuclear Medicine and Molecular Imaging}},
title = {{Longitudinal tau and metabolic PET imaging in relation to novel CSF tau measures in Alzheimer’s disease}},
url = {{http://dx.doi.org/10.1007/s00259-018-4242-6}},
doi = {{10.1007/s00259-018-4242-6}},
volume = {{46}},
year = {{2019}},
}