Poster No:
160
Submission Type:
Abstract Submission
Authors:
Marco Öchsner1, Matthias Brendel2, Nicolai Franzmeier3, Lena Trappmann4, Mirlind Zaganjori4, Ersin Ersoezlue4, Estrella Morenas-Rodriguez5, Selim Guersel4, Lena Burow4, Carolin Kurz4, Jan Haeckert4, Maia Tatò4, Julia Utecht4, Boris Papazov6, Oliver Pogarell4, Daniel Janowitz3, Katharina Buerger3, Michael Ewers3, Carla Palleis7, Endy Weidinger7, Gloria Biechele2, Sebastian Schuster2, Anika Finze2, Florian Eckenweber2, Rainer Rupprecht8, Axel Rominger2, Oliver Goldhardt9, Timo Grimmer9, Daniel Keeser4, Sophia Stoecklein6, Olaf Dietrich6, Peter Bartenstein2, Johannes Levin7, Günter Höglinger7, Robert Perneczky4, Boris-Stephan Rauchmann1
Institutions:
1Department of Neuroradiology, LMU University Hospital, Munich, Germany, 2Department of Nuclear Medicine, LMU University Hospital, Munich, Germany, 3Institute for Stroke and Dementia Research, LMU University Hospital, Munich, Germany, 4Department of Psychiatry and Psychotherapy, LMU University Hospital, Munich, Germany, 5Department of Biochemistry, LMU Munich, Munich, Germany, 6Department of Radiology, LMU University Hospital, Munich, Germany, 7Department of Neurology, LMU University Hospital, Munich, Germany, 8Department of Psychiatry and Psychotherapy, Regensburg University Hospital, Regensburg, Germany, 9Department of Psychiatry and Psychotherapy, TUM University Hospital, Munich, Germany
First Author:
Marco Öchsner
Department of Neuroradiology, LMU University Hospital
Munich, Germany
Co-Author(s):
Matthias Brendel
Department of Nuclear Medicine, LMU University Hospital
Munich, Germany
Nicolai Franzmeier
Institute for Stroke and Dementia Research, LMU University Hospital
Munich, Germany
Lena Trappmann
Department of Psychiatry and Psychotherapy, LMU University Hospital
Munich, Germany
Mirlind Zaganjori
Department of Psychiatry and Psychotherapy, LMU University Hospital
Munich, Germany
Ersin Ersoezlue
Department of Psychiatry and Psychotherapy, LMU University Hospital
Munich, Germany
Selim Guersel
Department of Psychiatry and Psychotherapy, LMU University Hospital
Munich, Germany
Lena Burow
Department of Psychiatry and Psychotherapy, LMU University Hospital
Munich, Germany
Carolin Kurz
Department of Psychiatry and Psychotherapy, LMU University Hospital
Munich, Germany
Jan Haeckert
Department of Psychiatry and Psychotherapy, LMU University Hospital
Munich, Germany
Maia Tatò
Department of Psychiatry and Psychotherapy, LMU University Hospital
Munich, Germany
Julia Utecht
Department of Psychiatry and Psychotherapy, LMU University Hospital
Munich, Germany
Boris Papazov
Department of Radiology, LMU University Hospital
Munich, Germany
Oliver Pogarell
Department of Psychiatry and Psychotherapy, LMU University Hospital
Munich, Germany
Daniel Janowitz
Institute for Stroke and Dementia Research, LMU University Hospital
Munich, Germany
Katharina Buerger
Institute for Stroke and Dementia Research, LMU University Hospital
Munich, Germany
Michael Ewers
Institute for Stroke and Dementia Research, LMU University Hospital
Munich, Germany
Carla Palleis
Department of Neurology, LMU University Hospital
Munich, Germany
Endy Weidinger
Department of Neurology, LMU University Hospital
Munich, Germany
Gloria Biechele
Department of Nuclear Medicine, LMU University Hospital
Munich, Germany
Sebastian Schuster
Department of Nuclear Medicine, LMU University Hospital
Munich, Germany
Anika Finze
Department of Nuclear Medicine, LMU University Hospital
Munich, Germany
Florian Eckenweber
Department of Nuclear Medicine, LMU University Hospital
Munich, Germany
Rainer Rupprecht
Department of Psychiatry and Psychotherapy, Regensburg University Hospital
Regensburg, Germany
Axel Rominger
Department of Nuclear Medicine, LMU University Hospital
Munich, Germany
Oliver Goldhardt
Department of Psychiatry and Psychotherapy, TUM University Hospital
Munich, Germany
Timo Grimmer
Department of Psychiatry and Psychotherapy, TUM University Hospital
Munich, Germany
Daniel Keeser
Department of Psychiatry and Psychotherapy, LMU University Hospital
Munich, Germany
Olaf Dietrich
Department of Radiology, LMU University Hospital
Munich, Germany
Peter Bartenstein
Department of Nuclear Medicine, LMU University Hospital
Munich, Germany
Günter Höglinger
Department of Neurology, LMU University Hospital
Munich, Germany
Robert Perneczky
Department of Psychiatry and Psychotherapy, LMU University Hospital
Munich, Germany
Introduction:
Microglial activation is increasingly recognised as a key feature of progression in the Alzheimer's disease spectrum (ADS). While they may have a protective function, by aiding in the clearance of amyloid β (Aβ), sustained microglial activation induces a predominantly neurotoxic phenotype, disrupting neural networks. Recent evidence suggests that the spread of microglia parallels that of tau accumulation along highly connected brain regions. However, it remains elusive whether microglial activation in the ADS is a response to pathological protein accumulation, or directly influences this accumulation. We examined (a) how microglial activation changes differ between ADS patients and controls over time, (b) whether these changes are linked to tau levels, and (c) whether they affect the relationship between tau and functional connectivity.
Methods:
As part of the longitudinal ActiGliA prospective cohort study, ADS (n=33, defined by CSF Aβ42/Aβ40 ratio or an Aβ PET composite of ADS vulnerable brain regions) and HC (n=26) underwent [18F]GE-180 imaging to assess microglial activation and resting-state fMRI to determine brain connectivity, alongside structural T1 MRI. Preprocessing of fMRI data was performed using fMRIPrep version 1.2.1, and atlas-based connectivity values were calculated as r-to-z transformed pairwise correlations of time series after filtering, smoothing, and applying confound regressors. After 18 months, a subset of participants received follow-up TAU-PET ([18F]Flutemetamol) and TSPO-PET imaging. These were all processed to allow for ROI-based comparisons using the Schaefer200 atlas. PET standardized uptake value ratios (SUVRs) were then intensity-normalized to the inferior cerebellar gray matter, and follow-up-to-baseline SUVR ratios were calculated for TSPO-PET. Group differences in changes in TSPO-PET SUVRs and their association with TAU-PET levels at follow-up were assessed using a Mann-Whitney U test and Cliff's Delta. A linear regression model was fit to determine whether TSPO SUVRs predicted TAU SUVR levels and whether this relationship was mediated by changes in TSPO SUVRs. Finally, we evaluated how TSPO SUVRs and their longitudinal changes mediated the association between functional connectivity and TAU SUVRs with a Spearman correlation.
Results:
Microglial activation, as measured by TSPO-PET SUVR, increased from baseline to follow-up in ADS (mean change 1.01, SD 0.02), when compared to HC (mean change 0.95, SD 0.03; d=0.87, MWU statistic=37329.0, p<0.001). In ADS, regions with lower TSPO change exhibited marginally higher TAU levels (median SUVR 1.26 vs 1.14; d=0.19, MWU=5430.0, p=0.03), and a linear regression (AdjR2=0.47, F(1,198)=174.95, p<0.001) showed TSPO SUVRs at follow-up significantly predicting TAU SUVRs (β=0.79 [0.67, 0.91], p<0.001). When performing separate regressions for regions with increasing TSPO SUVRs, the regression (AdjR2=0.49, F(1,127)=125.9, p<0.001) shows an increased coefficient for TAU SUVRs (β=1.098 [0.905, 1.292], p<0.001) when compared to the regression (AdjR2=0.51, F(1,69)=73.75, p<0.001) for regions with decreasing TSPO SUVRs (β=0.597 [0.458, 0.735], p<0.001). In HC these trends are opposite. Finally, the association between functional connectivity and TAU-PET SUVRs was negatively correlated with TSPO-PET SUVR changes in ADS (ρ=-0.25, p<0.001), while in HC, this correlation was positive (ρ=0.23, p=0.001).
Conclusions:
Our findings indicate that microglial activation, as measured by TSPO-PET, tends to increase in ADS when compared to HC. In ADS, higher tau accumulation was observed in regions with reduced microglial activation, contrasting with the observations for HC, which may be related to differing levels of TAU, Aβ, and microglial activation. Furthermore, the spread of microglial activation mirrors tau propagation in highly connected regions, and the strength of this association is modulated by the extent of TSPO change; yet, the direction of this association is opposite in ADS and HC.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Lifespan Development:
Aging 2
Modeling and Analysis Methods:
PET Modeling and Analysis
Keywords:
Aging
Degenerative Disease
Positron Emission Tomography (PET)
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
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Was this research conducted in the United States?
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
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Please indicate which methods were used in your research:
PET
Functional MRI
Structural MRI
Neuropsychological testing
For human MRI, what field strength scanner do you use?
3.0T
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FSL
Free Surfer
Provide references using APA citation style.
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