Rauchmann, Boris-Stephan and Brendel, Matthias and Franzmeier, Nicolai and Trappmann, Lena and Zaganjori, Mirlind and Ersoezlue, Ersin and Morenas-Rodriguez, Estrella and Guersel, Selim and Burow, Lena and Kurz, Carolin and Haeckert, Jan and Tato, Maia and Utecht, Julia and Papazov, Boris and Pogarell, Oliver and Janowitz, Daniel and Buerger, Katharina and Ewers, Michael and Palleis, Carla and Weidinger, Endy and Biechele, Gloria and Schuster, Sebastian and Finze, Anika and Eckenweber, Florian and Rupprecht, Rainer and Rominger, Axel and Goldhardt, Oliver and Grimmer, Timo and Keeser, Daniel and Stoecklein, Sophia and Dietrich, Olaf and Bartenstein, Peter and Levin, Johannes and Hoglinger, Gunter and Perneczky, Robert (2022) Microglial Activation and Connectivity in Alzheimer Disease and Aging. ANNALS OF NEUROLOGY, 92 (5). pp. 768-781. ISSN 0364-5134, 1531-8249
Full text not available from this repository. (Request a copy)Abstract
Objective Alzheimer disease (AD) is characterized by amyloid beta (A beta) plaques and neurofibrillary tau tangles, but increasing evidence suggests that neuroinflammation also plays a key role, driven by the activation of microglia. A beta and tau pathology appear to spread along pathways of highly connected brain regions, but it remains elusive whether microglial activation follows a similar distribution pattern. Here, we assess whether connectivity is associated with microglia activation patterns. Methods We included 32 A beta-positive early AD subjects (18 women, 14 men) and 18 A beta-negative age-matched healthy controls (10 women, 8 men) from the prospective ActiGliA (Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer's Disease) study. All participants underwent microglial activation positron emission tomography (PET) with the third-generation mitochondrial 18 kDa translocator protein (TSPO) ligand [F-18]GE-180 and magnetic resonance imaging (MRI) to measure resting-state functional and structural connectivity. Results We found that inter-regional covariance in TSPO-PET and standardized uptake value ratio was preferentially distributed along functionally highly connected brain regions, with MRI structural connectivity showing a weaker association with microglial activation. AD patients showed increased TSPO-PET tracer uptake bilaterally in the anterior medial temporal lobe compared to controls, and higher TSPO-PET uptake was associated with cognitive impairment and dementia severity in a disease stage-dependent manner. Interpretation Microglial activation distributes preferentially along highly connected brain regions, similar to tau pathology. These findings support the important role of microglia in neurodegeneration, and we speculate that pathology spreads throughout the brain along vulnerable connectivity pathways. ANN NEUROL 2022
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VIVO RADIOLIGAND BINDING; TRANSLOCATOR PROTEIN; SOLUBLE TREM2; NEUROINFLAMMATION; TAU; BRAIN; BIOMARKER; DEPLETION; CERAD; BETA; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Jan 2024 14:50 |
| Last Modified: | 29 Jan 2024 14:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58615 |
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