Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF
- Description
Lysosomal failure plays an important role in the pathogenesis of many congenital neurodegenerative disorders, such as Alzheimer’s disease (AD) and Down syndrome (DS). This study showed that lysosomal dysfunction in DS requires the extra gene copy of amyloid precursor protein (APP) and is specifically mediated by the β cleaved carboxy terminal fragment of APP (APP-βCTF). In primary fibroblasts from individuals with DS, lysosomal degradation of autophagic and endocytic substrates is selectively impaired, which causes them to accumulate in enlarged autolysosomes/lysosomes. The dataset contains RNA sequencing data. This study revealed that modest elevation of endogenous APP in DS is sufficient to induce lysosomal disruption and that a rise in levels of APP-βCTF in lysosomes is the cause of the disruption.
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- Restrictions
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Free to All
- Instructions
- The raw and processed data have been deposited in Gene Expression Omnibus (GEO).
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