ArticleThe Journal of experimental medicine2021
An APP ectodomain mutation outside of the Aβ domain promotes Aβ production in vitro and deposition in vivo.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- From cell to disease: Regulatory networks and mechanisms of super‑enhancers in aging (Review).Molecular medicine reports · 2026Review
- EV-transferred miR-7111-3p inhibits malignant phenotypes and tumor growth in nasopharyngeal carcinoma via targeting APP-regulated epithelial-mesenchymal transition.Journal of translational medicine · 2026Article
- Recent Advances and Future Directions in Alzheimer's Disease Genetic Research.International journal of molecular sciences · 2025Review
- The pathogenic APP N-terminal Val225Ala mutation alters tau protein liquid-liquid phase separation and exacerbates synaptic damage.Molecular psychiatry · 2025Article
- Identification and characterization of variants in PSEN1, PSEN2, and APP genes in Chinese patients with early-onset Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- A Survey on Computational Methods in Drug Discovery for Neurodegenerative Diseases.Biomolecules · 2024Review
- Genomic Insights into Dementia: Precision Medicine and the Impact of Gene-Environment Interaction.Aging and disease · 2024Review
- Genetic and Epigenetic Biomarkers Linking Alzheimer's Disease and Age-Related Macular Degeneration.International journal of molecular sciences · 2024Review
- Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.Aging and disease · 2024Review
- Can Genetic Markers Predict the Sporadic Form of Alzheimer's Disease? An Updated Review on Genetic Peripheral Markers.International journal of molecular sciences · 2023Review
- Alzheimer's Disease: An Updated Overview of Its Genetics.International journal of molecular sciences · 2023Review
- SPIN90 Deficiency Ameliorates Amyloid β Accumulation by Regulating APP Trafficking in AD Model Mice.International journal of molecular sciences · 2022Article
- Neuroinflammation represents a common theme amongst genetic and environmental risk factors for Alzheimer and Parkinson diseases.Journal of neuroinflammation · 2022Review
- MDGA1 negatively regulates amyloid precursor protein-mediated synapse inhibition in the hippocampus.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Redox signaling and metabolism in Alzheimer's disease.Frontiers in aging neuroscience · 2022Review
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10 authors.
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Abstract
Familial Alzheimer's disease (FAD)-linked mutations in the APP gene occur either within the Aβ-coding region or immediately proximal and are located in exons 16 and 17, which encode Aβ peptides. We have identified an extremely rare, partially penetrant, single nucleotide variant (SNV), rs145081708, in APP that corresponds to a Ser198Pro substitution in exon 5. We now report that in stably transfected cells, expression of APP harboring the S198P mutation (APPS198P) leads to elevated production of Aβ peptides by an unconventional mechanism in which the folding and exit of APPS198P from the endoplasmic reticulum is accelerated. More importantly, coexpression of APP S198P and the FAD-linked PS1ΔE9 variant in the brains of male and female transgenic mice leads to elevated steady-state Aβ peptide levels and acceleration of Aβ deposition compared with age- and gender-matched mice expressing APP and PS1ΔE9. This is the first AD-linked mutation in APP present outside of exons 16 and 17 that enhances Aβ production and deposition.
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