SWI and phase imaging reveal intracranial calcifications in the P301L mouse model of human tauopathy.
- Ni R Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Vladimir-Prelog-Weg 4, Wolfgang-Pauli-Strasse 27, 8093, Zurich, Switzerland.
- Zarb Y Zurich Neuroscience Center, University of Zurich, Zurich, Switzerland.
- Kuhn GA Department of Health Sciences and Technology, Institute for Biomechanics, ETH Zurich, Leopold-Ruzicka-Weg 4, 8093, Zurich, Switzerland.
- Müller R Department of Health Sciences and Technology, Institute for Biomechanics, ETH Zurich, Leopold-Ruzicka-Weg 4, 8093, Zurich, Switzerland.
- Yundung Y Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Vladimir-Prelog-Weg 4, Wolfgang-Pauli-Strasse 27, 8093, Zurich, Switzerland.
- Nitsch RM Institute for Regenerative Medicine, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.
- Kulic L Institute for Regenerative Medicine, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.
- Keller A Zurich Neuroscience Center, University of Zurich, Zurich, Switzerland.
- Klohs J Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Vladimir-Prelog-Weg 4, Wolfgang-Pauli-Strasse 27, 8093, Zurich, Switzerland. klohs@biomed.ee.ethz.ch.
- 2020-05-30
Published in:
- Magma (New York, N.Y.). - 2020
Alzheimer’s disease
Calcification
Phase imaging
Susceptibility weighted imaging
Tauopathy
Transgenic mouse model
English
OBJECTIVE
Brain calcifications are associated with several neurodegenerative diseases. Here, we describe the occurrence of intracranial calcifications as a new phenotype in transgenic P301L mice overexpressing four repeat tau, a model of human tauopathy.
MATERIALS AND METHODS
Thirty-six P301L mice (Thy1.2) and ten age-matched non-transgenic littermates of different ages were assessed. Gradient echo data were acquired in vivo and ex vivo at 7 T and 9.4 T for susceptibility-weighted imaging (SWI) and phase imaging. In addition, ex vivo micro-computed tomography (μCT) was performed. Histochemistry and immunohistochemistry were used to investigate the nature of the imaging lesions.
RESULTS
SW images revealed regional hypointensities in the hippocampus, cortex, caudate nucleus, and thalamus of P301L mice, which in corresponding phase images indicated diamagnetic lesions. Concomitantly, µCT detected hyperdense lesions, though fewer lesions were observed compared to MRI. Diamagnetic susceptibility lesions in the hippocampus increased with age. The immunochemical staining of brain sections revealed osteocalcin-positive deposits. Furthermore, intra-neuronal and vessel-associated osteocalcin-containing nodules co-localized with phosphorylated-tau (AT8 and AT100) in the hippocampus, while vascular osteocalcin-containing nodules were detected in the thalamus in the absence of phosphorylated-tau deposition.
DISCUSSION
SWI and phase imaging sensitively detected intracranial calcifications in the P301L mouse model of human tauopathy.
Brain calcifications are associated with several neurodegenerative diseases. Here, we describe the occurrence of intracranial calcifications as a new phenotype in transgenic P301L mice overexpressing four repeat tau, a model of human tauopathy.
MATERIALS AND METHODS
Thirty-six P301L mice (Thy1.2) and ten age-matched non-transgenic littermates of different ages were assessed. Gradient echo data were acquired in vivo and ex vivo at 7 T and 9.4 T for susceptibility-weighted imaging (SWI) and phase imaging. In addition, ex vivo micro-computed tomography (μCT) was performed. Histochemistry and immunohistochemistry were used to investigate the nature of the imaging lesions.
RESULTS
SW images revealed regional hypointensities in the hippocampus, cortex, caudate nucleus, and thalamus of P301L mice, which in corresponding phase images indicated diamagnetic lesions. Concomitantly, µCT detected hyperdense lesions, though fewer lesions were observed compared to MRI. Diamagnetic susceptibility lesions in the hippocampus increased with age. The immunochemical staining of brain sections revealed osteocalcin-positive deposits. Furthermore, intra-neuronal and vessel-associated osteocalcin-containing nodules co-localized with phosphorylated-tau (AT8 and AT100) in the hippocampus, while vascular osteocalcin-containing nodules were detected in the thalamus in the absence of phosphorylated-tau deposition.
DISCUSSION
SWI and phase imaging sensitively detected intracranial calcifications in the P301L mouse model of human tauopathy.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1007/s10334-020-00855-3
- PMID 32468149
- Persistent URL
- https://sonar.ch/global/documents/185310
Statistics
Document views: 18
File downloads:
- Full-text: 0