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  PET/MRI delivers multimodal brain signature in Alzheimer's disease with de novo PSEN1 mutation

Aghakhanyan, G., Saur, D., Rullmann, M., Weise, C. M., Schroeter, M. L., Marek, K., et al. (2021). PET/MRI delivers multimodal brain signature in Alzheimer's disease with de novo PSEN1 mutation. Current Alzheimer Research, 18(2), 178-184. doi:10.2174/1567205018666210414111536.

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 Creators:
Aghakhanyan, Gayane1, Author
Saur, Dorothee2, Author
Rullmann, Michael1, Author
Weise, Christopher M3, Author
Schroeter, Matthias L.4, Author              
Marek, Ken5, Author
Jamra, Rami Abou6, Author
Tiepolt, Solveig1, Author
Strauss, Maria7, Author
Scherlach, Cordula3, Author
Hoffmann, Karl-Titus3, Author
Sabri, Osama1, Author
Classen, Joseph2, Author
Barthel, Henryk1, Author
Affiliations:
1Department of Nuclear Medicine, University of Leipzig, Germany, ou_persistent22              
2Department of Neurology, University Hospital Leipzig, Germany, ou_persistent22              
3Department of Neuroradiology, University of Leipzig, Germany, ou_persistent22              
4Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
5Invicro, New Haven, CT, USA, ou_persistent22              
6Institute of Human Genetics, University of Leipzig, Germany, ou_persistent22              
7Department of Psychiatry and Psychotherapy, University Hospital Leipzig, Germany, ou_persistent22              

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Free keywords: Amyloid PET; DTI; PET/MRI; PSEN1; Autosomal dominant Alzheimer’s disease; Hippocampus; rs-fMRI; tau PET
 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.

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Language(s): eng - English
 Dates: 2021-06-02
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.2174/1567205018666210414111536
PMID: 33855944
 Degree: -

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Title: Current Alzheimer Research
Source Genre: Journal
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Publ. Info: Hilversum : Bentham Science
Pages: - Volume / Issue: 18 (2) Sequence Number: - Start / End Page: 178 - 184 Identifier: ISSN: 1875-5828
CoNE: https://pure.mpg.de/cone/journals/resource/1875-5828