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. 2018 Nov 2:10:782-790.
doi: 10.1016/j.dadm.2018.10.003. eCollection 2018.

CSF total tau levels are associated with hippocampal novelty irrespective of hippocampal volume

Emrah Düzel  1   2   3 , David Berron  1   2 , Hartmut Schütze  1   2 , Arturo Cardenas-Blanco  1   2 , Coraline Metzger  1   2   4 , Matthew Betts  2 , Gabriel Ziegler  1   2 , Yi Chen  1   2 , Laura Dobisch  2 , Daniel Bittner  2   5 , Wenzel Glanz  2 , Martin Reuter  6 , Annika Spottke  6   7 , Janna Rudolph  6 , Frederic Brosseron  6   8 , Katharina Buerger  9   10 , Daniel Janowitz  10 , Klaus Fliessbach  6 , Michael Heneka  6   8 , Christoph Laske  11   12 , Martina Buchmann  11   12 , Peter Nestor  2 , Oliver Peters  13   14 , Dominik Diesing  14 , Siyao Li  14 , Josef Priller  13   15 , Eike Jakob Spruth  15 , Slawek Altenstein  13 , Alfredo Ramirez  16 , Anja Schneider  6   8 , Barbara Kofler  8 , Oliver Speck  17 , Stefan Teipel  18   19 , Ingo Kilimann  18   19 , Martin Dyrba  18 , Jens Wiltfang  20   21 , Claudia Bartels  20   21 , Steffen Wolfsgruber  6 , Michael Wagner  6   8 , Frank Jessen  6   16
Affiliations

CSF total tau levels are associated with hippocampal novelty irrespective of hippocampal volume

Emrah Düzel et al. Alzheimers Dement (Amst). .

Abstract

Introduction: We examined the association between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, neural novelty responses, and brain volume in predementia old age.

Methods: We conducted a cross-sectional analysis of the observational, multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Seventy-six participants completed task functional magnetic resonance imaging and provided CSF (40 cognitively unimpaired, 21 experiencing subjective cognitive decline, and 15 with mild cognitive impairment). We assessed the correlation between CSF biomarkers and whole-brain functional magnetic resonance imaging novelty responses to scene images.

Results: Total tau levels were specifically and negatively associated with novelty responses in the right amygdala and right hippocampus. Mediation analyses showed no evidence that these associations were dependent on the volume of hippocampus/amygdala. No relationship was found between phosphorylated-tau or Aβ42 levels and novelty responses.

Discussion: Our data show that CSF levels of total tau are associated with anatomically specific reductions in novelty processing, which cannot be fully explained by atrophy.

Keywords: Alzheimer's disease (AD); Apolipoprotein E (APOE); Aβ42; Cerebrospinal fluid (CSF); Longitudinal; Magnetic resonance imaging (MRI); Mild cognitive impairment (MCI); Positron emission tomography (PET); Subjective cognitive decline (SCD); Tau.

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Figures

Fig. 1
Fig. 1
Correlation between CSF levels of total tau (pg/mL) and recognition memory accuracy (dprime) for the novel scenes presented during task-fMRI. Color codes indicate healthy controls (blue), subjective complainers (subjective cognitive decline, green), and individuals with mild cognitive impairment (mild cognitive impairment, orange).
Fig. 2
Fig. 2
Novelty activations and regression analyses. (A) Group-level contrast depicting increased BOLD responses to novel as compared to familiar scenes in the entire sample of 76 participants (depicted at P < .001 uncorrected, k = 400 voxels). Left panel shows entire activation map as a glass brain. Right panel depicts activation on group template (left is left). (B) Whole-brain regression analysis with CSF total tau levels. CSF total tau levels correlate selectively with novelty responses in the amygdala (left panel) and the hippocampus (right panel). Covariates were MRI sites (6 sites), age, gender, and Aβ42 levels. Abbreviations: CSF, cerebrospinal fluid; MRI, magnetic resonance imaging.
Fig. 3
Fig. 3
Mediation analyses. Total tau levels have a significant association with hippocampus + amygdala volume. The volume of hippocampus + amygdala, however, does not have a significant association with novelty. As expected (given the selection of the novelty cluster), there is also a significant influence on novelty responses in the hippocampus/amygdala clusters. More importantly, the direct effect of total tau levels on novelty responses remains significant after controlling for hippocampus/amygdala volume.
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