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Wurster, Isabel; Quadalti, Corinne; Rossi, Marcello; Hauser, Ann-Kathrin; Deuschle, Christian; Schulte, Claudia; Waniek, Katharina; Lachmann, Ingolf; la Fougere, Christian; Doppler, Kathrin; Gasser, Thomas; Bender, Benjamin; Parchi, Piero; Brockmann, Kathrin

Linking the phenotype of SNCA Triplication with PET-MRI imaging pattern and alpha-synuclein CSF seeding

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  • Medientyp: E-Artikel
  • Titel: Linking the phenotype of SNCA Triplication with PET-MRI imaging pattern and alpha-synuclein CSF seeding
  • Beteiligte: Wurster, Isabel; Quadalti, Corinne; Rossi, Marcello; Hauser, Ann-Kathrin; Deuschle, Christian; Schulte, Claudia; Waniek, Katharina; Lachmann, Ingolf; la Fougere, Christian; Doppler, Kathrin; Gasser, Thomas; Bender, Benjamin; Parchi, Piero; Brockmann, Kathrin
  • Erschienen: Springer Science and Business Media LLC, 2022
  • Erschienen in: npj Parkinson's Disease
  • Sprache: Englisch
  • DOI: 10.1038/s41531-022-00379-8
  • ISSN: 2373-8057
  • Schlagwörter: Cellular and Molecular Neuroscience ; Neurology (clinical) ; Neurology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Lewy-body pathology with aggregation of abnormal conformations of the protein alpha-synuclein (α-Syn) represent the histopathological hallmarks of Parkinson’s disease (PD). Genetic prototypes such as PD due to mutations in the <jats:italic>alpha-synuclein</jats:italic> gene (<jats:italic>SNCA</jats:italic>) offer the opportunity to evaluate α-Syn-related profiles in patient-derived biomaterial. We identified a family with a <jats:italic>SNCA</jats:italic> triplication and assessed the index patient for CSF α-Syn seeding capacity and levels of total α-Syn along with other neurodegenerative CSF markers (Aβ<jats:sub>1-42</jats:sub>, total-Tau, phospho-Tau, NFL). As no published CSF data in patients with <jats:italic>SNCA</jats:italic> triplication are available, we descriptively compared his CSF profiles to those of sporadic PD patients and PD patients with <jats:italic>GBA</jats:italic> mutations as these are also specifically associated with prominent α-Syn pathology. Additionally, skin biopsies with staining for phospho-α-Syn were done. To assess cerebral glucose metabolism and brain atrophy combined positron emission tomography and magnetic resonance imaging ([<jats:sup>18</jats:sup>F]FDG-PET/MRI) was performed. Age at onset was 24 years and motor impairment was accompanied by prominent non-motor symptoms with early development of dementia, depression, REM sleep behavior disorder, hyposmia, and dysautonomia. Correspondingly, PET-MRI showed hypometabolism and atrophy in frontal, temporoparietal and occipital regions. CSF levels of total α-Syn were threefold higher and RT-QuIC showed remarkable α-Syn seeding activity in all kinetic categories in the SNCA<jats:sub>Triplication</jats:sub> patient compared to patients with <jats:italic>GBA</jats:italic> mutations. Our results are consistent with findings that not only mutant forms but also overexpression of the wild-type α-Syn protein lead to PD and PD dementia and show a striking CSF α-Syn seeding profile, thus substantiating the role of RT-QuIC as a specific in vivo biomarker of α-Syn brain pathology.</jats:p>
  • Zugangsstatus: Freier Zugang