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

Emrah Düzel; David Berron; Hartmut Schütze; Arturo Cardenas-Blanco; Coraline Metzger; Matthew Betts; Gabriel Ziegler; Yi Chen; Laura Dobisch; Daniel Bittner; Wenzel Glanz; Martin Reuter; Annika Spottke; Janna Rudolph; Frederic Brosseron; Katharina Buerger; Daniel Janowitz; Klaus Fliessbach; Michael Heneka; Christoph Laske; Martina Buchmann; Peter Nestor; Oliver Peters; Dominik Diesing; Siyao Li; Josef Priller; Eike Jakob Spruth; Slawek Altenstein; Alfredo Ramirez; Anja Schneider; Barbara Kofler; Oliver Speck; Stefan Teipel; Ingo Kilimann; Martin Dyrba; Jens Wiltfang; Claudia Bartels; Steffen Wolfsgruber; Michael Wagner; Frank Jessen

doi:10.1016/j.dadm.2018.10.003

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

Alzheimers Dement (Amst). 2018 Nov 2:10:782-790. doi: 10.1016/j.dadm.2018.10.003. eCollection 2018.

Authors

Emrah Düzel^{1

2

3}, David Berron^{1

2}, Hartmut Schütze^{1

2}, Arturo Cardenas-Blanco^{1

2}, Coraline Metzger^{1

2

4}, Matthew Betts², Gabriel Ziegler^{1

2}, Yi Chen^{1

2}, Laura Dobisch², Daniel Bittner^{2

5}, Wenzel Glanz², Martin Reuter⁶, Annika Spottke^{6

7}, Janna Rudolph⁶, Frederic Brosseron^{6

8}, Katharina Buerger^{9

10}, Daniel Janowitz¹⁰, Klaus Fliessbach⁶, Michael Heneka^{6

8}, Christoph Laske^{11

12}, Martina Buchmann^{11

12}, Peter Nestor², Oliver Peters^{13

14}, Dominik Diesing¹⁴, Siyao Li¹⁴, Josef Priller^{13

15}, Eike Jakob Spruth¹⁵, Slawek Altenstein¹³, Alfredo Ramirez¹⁶, Anja Schneider^{6

8}, Barbara Kofler⁸, Oliver Speck¹⁷, Stefan Teipel^{18

19}, Ingo Kilimann^{18

19}, Martin Dyrba¹⁸, Jens Wiltfang^{20

21}, Claudia Bartels^{20

21}, Steffen Wolfsgruber⁶, Michael Wagner^{6

8}, Frank Jessen^{6

16}

Affiliations

¹ Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
² German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
³ Institute of Cognitive Neuroscience, Univ. College London, London, UK.
⁴ Department of Psychiatry and Psychotherapy, University Hospital Magdeburg, Medical Faculty, Magdeburg, Germany.
⁵ Clinic for Neurology, University Hospital Magdeburg, Medical Faculty, Magdeburg, Germany.
⁶ German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
⁷ Department of Neurology, University of Bonn, Bonn, Germany.
⁸ Department of Neurodegeneration and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
⁹ German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
¹⁰ Institute for Stroke and Dementia Research, University Hospital, Munich, Germany.
¹¹ German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
¹² Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
¹³ German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
¹⁴ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Psychiatry and Psychotherapy, Berlin, Germany.
¹⁵ Department of Psychiatry and Psychotherapy, Berlin, Germany.
¹⁶ Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany.
¹⁷ Department of Biomagnetical Resonance, Magdeburg, Germany.
¹⁸ German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
¹⁹ Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany.
²⁰ German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany.
²¹ Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen, Germany.

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.