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Vöglein, Jonathan; Arzberger, Thomas; Willem, Michael; Trambauer, Johannes; Dieterich, Marianne; Biskup, Saskia; Guidici, Camilla; Brendel, Matthias; Roeber, Sigrun; Danek, Adrian; Steiner, Harald; Herms, Jochen; Haass, Christian; Levin, Johannes

Neuropathological characteristics associated with a recently identified rare PSEN1 deletion mutation (F175del) : Human neuropathology/proteinopathies : Human neuropathology/proteinopathies

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  • Medientyp: E-Artikel
  • Titel: Neuropathological characteristics associated with a recently identified rare PSEN1 deletion mutation (F175del) : Human neuropathology/proteinopathies : Human neuropathology/proteinopathies
  • Beteiligte: Vöglein, Jonathan; Arzberger, Thomas; Willem, Michael; Trambauer, Johannes; Dieterich, Marianne; Biskup, Saskia; Guidici, Camilla; Brendel, Matthias; Roeber, Sigrun; Danek, Adrian; Steiner, Harald; Herms, Jochen; Haass, Christian; Levin, Johannes
  • Erschienen: Wiley, 2020
  • Erschienen in: Alzheimer's & Dementia
  • Sprache: Englisch
  • DOI: 10.1002/alz.045048
  • ISSN: 1552-5260; 1552-5279
  • Schlagwörter: Psychiatry and Mental health ; Cellular and Molecular Neuroscience ; Geriatrics and Gerontology ; Neurology (clinical) ; Developmental Neuroscience ; Health Policy ; Epidemiology
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The novel <jats:italic>PSEN1</jats:italic>single amino acid deletion mutation F175del causes autosomal dominant Alzheimer disease (ADAD) in the late thirties. <jats:italic>In vitro</jats:italic>F175del features an unusual pattern of APP fragments including an increased production of Aβ39. This Aβ species was found particularly in brain vessels and therefore may contribute to the development of cerebral amyloid angiopathy (CAA).</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>Neuropathological examination was performed in a patient with ADAD caused by <jats:italic>PSEN1</jats:italic>F175del who died at the age of 45 years. Clinical, neuropsychological, genetic and biomarker findings in this patient as well effects of the <jats:italic>PSEN1</jats:italic>deletion mutation on Aβ processing were described before (Vöglein et al, Neurobiology of Aging, 2019).</jats:p></jats:sec><jats:sec><jats:title>Result</jats:title><jats:p>Copious cored/compact and diffuse Aβ plaques were found in the cerebral cortex. Interestingly, there were plentiful streaky and several cored/compact and diffuse Aβ plaques also in the cerebellum. A large number of cortical neuropil threads and neurons with fibrillary cytoplasmatic tau aggregates as well as several neuritic plaques were detected (ABC score: A3/B3/C3). CAA with Aβ depositions in the leptomeningeal and cortical vessel walls was detected (Thal phase 2). Furthermore, several Lewy bodies and Lewy neurites were found in the cerebral cortex (Braak stage 6).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The neuropathological hallmarks of AD, Aβ plaques and neurofibrillary degeneration, were present in <jats:italic>PSEN1</jats:italic> F175del associated ADAD. CAA was found that could be in causal connection with the enhanced Aβ 39 generation caused by the mutation as shown in cell culture. Further, an unusually high cerebellar Aβ burden was detected. In summary, we provide neuropathological characteristics of ADAD caused by <jats:italic>PSEN1</jats:italic> F175del and potentially unveiled an effect of an altered Aβ processing that was shown <jats:italic>in vitro</jats:italic> on brain pathology.</jats:p></jats:sec>