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PET/MRI Delivers Multimodal Brain Signature in Alzheimer’s Disease with De Novo PSEN1 Mutation

[ Vol. 18 , Issue. 2 ]

Author(s):

Gayane Aghakhanyan, Dorothee Saur, Michael Rullmann, Christopher M. Weise, Matthias L. Schroeter, Ken Marek, Rami Abou Jamra, Solveig Tiepolt, Maria Strauss, Cordula Scherlach, Karl-Titus Hoffmann, Osama Sabri, Joseph Classen and Henryk Barthel*   Pages 178 - 184 ( 7 )

Abstract:


Background: Little is known so far about the brain phenotype and the spatial interplay of different Alzheimer’s disease (AD) biomarkers with structural and functional brain connectivity in the early phase of autosomal-dominant AD (ADAD). Multimodal PET/MRI might be suitable to fill this gap.

Material and Methods: We presented a 31-year-old male patient without a family history of dementia with progressive worsening of memory and motor function. Two separate sessions of 3T PET/MRI acquisitions were arranged with the ß-amyloid tracer [18F]Florbetaben and the secondgeneration tau tracer [18F]PI-2620. Simultaneously acquired MRI consisted of high-resolution 3D T1, diffusion-tensor imaging (DTI), and resting-state fMRI. PET/MRI data were compared with ten age-matched healthy controls.

Results: Widespread β-amyloid depositions were found in cortical regions, and striatum (Thal stage III) along with tau pathology restricted to the mesial-temporal structures (Braak stage III/IV). Volumetric/shape analysis of subcortical structures revealed atrophy of the hippocampal-amygdala complex. In addition, cortical thinning was detected in the right middle temporal pole. Alterations of multiple DTI indices were noted in the major white matter fiber bundles, together with disruption of default mode and sensory-motor network functional connectivity. Molecular genetic analysis by next-generation sequencing revealed a heterozygote missense pathogenic variant of the PSEN1 (Met233Val).

Conclusion : Multimodal PET/MR imaging is able to deliver, in a one-stop-shop approach, an array of molecular, structural and functional brain information in AD due to de novo pathogenic variant, which can be studied for spatial interplay and might provide a rationale for initiating anti- amyloid/tau therapeutic approaches.

Keywords:

Amyloid PET, tau PET, autosomal dominant Alzheimer’s disease, hippocampus, PET/MRI, PSEN1, rs-fMRI, DTI

Affiliation:

Department of Nuclear Medicine, University of Leipzig, Leipzig, Department of Neurology, University of Leipzig, Leipzig, Department of Nuclear Medicine, University of Leipzig, Leipzig, Department of Neuroradiology, University Hospital Leipzig, Leipzig, Max Planck Institute for Human Cognitive and Brain Sciences, Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Invicro, New Haven, CT, Institute for Human Genetics, University Hospital Leipzig, Leipzig, Department of Nuclear Medicine, University of Leipzig, Leipzig, Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Department of Neuroradiology, University Hospital Leipzig, Leipzig, Department of Neuroradiology, University Hospital Leipzig, Leipzig, Department of Nuclear Medicine, University of Leipzig, Leipzig, Department of Neurology, University of Leipzig, Leipzig, Department of Nuclear Medicine, University of Leipzig, Leipzig



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