دورية أكاديمية
The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid β fibril formation.
| العنوان: | The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid β fibril formation. |
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| المؤلفون: | Pagnon de la Vega, María, Giedraitis, Vilmantas, Alafuzoff, Irina, Nilsson, Lars N G, Erlandsson, Anna, Willbold, Dieter, Müller, Stephan A, Schröder, Gunnar F, Hanrieder, Jörg, Lichtenthaler, Stefan, Lannfelt, Lars, Sehlin, Dag, Michno, Wojciech, Ingelsson, Martin, Kilander, Lena, Güner, Gökhan, Zielinski, Mara, Löwenmark, Malin, Brundin, RoseMarie, Danfors, Torsten, Söderberg, Linda |
| المصدر: | Science translational medicine 13(606), eabc6184 (2021). doi:10.1126/scitranslmed.abc6184 |
| بيانات النشر: | AAAS |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | info:eu-repo/classification/ddc/500, Alzheimer Disease: genetics, Amyloid Precursor Protein Secretases: metabolism, Amyloid beta-Peptides: metabolism, Amyloid beta-Protein Precursor: genetics, Amyloid beta-Protein Precursor: metabolism, Brain: metabolism, Humans, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Amyloid Precursor Protein Secretases |
| جغرافية الموضوع: | DE |
| الوصف: | Point mutations in the amyloid precursor protein gene (APP) cause familial Alzheimer's disease (AD) by increasing generation or altering conformation of amyloid β (Aβ). Here, we describe the Uppsala APP mutation (Δ690-695), the first reported deletion causing autosomal dominant AD. Affected individuals have an age at symptom onset in their early forties and suffer from a rapidly progressing disease course. Symptoms and biomarkers are typical of AD, with the exception of normal cerebrospinal fluid (CSF) Aβ42 and only slightly pathological amyloid-positron emission tomography signals. Mass spectrometry and Western blot analyses of patient CSF and media from experimental cell cultures indicate that the Uppsala APP mutation alters APP processing by increasing β-secretase cleavage and affecting α-secretase cleavage. Furthermore, in vitro aggregation studies and analyses of patient brain tissue samples indicate that the longer form of mutated Aβ, AβUpp1-42Δ19-24, accelerates the formation of fibrils with unique polymorphs and their deposition into amyloid plaques in the affected brain. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/issn/1946-6234; info:eu-repo/semantics/altIdentifier/pmid/pmid:34380771; info:eu-repo/semantics/altIdentifier/issn/1946-6242; https://pub.dzne.de/record/162825Test; https://pub.dzne.de/search?p=id:%22DZNE-2021-01480%22Test |
| الإتاحة: | https://doi.org/10.1126/scitranslmed.abc6184Test https://pub.dzne.de/record/162825Test https://pub.dzne.de/search?p=id:%22DZNE-2021-01480%22Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.63C6F3EC |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |