Spatial–Temporal Mapping Reveals the Golgi as the Major Processing Site for the Pathogenic Swedish APP Mutation: Familial APP Mutant Shifts the Major APP Processing Site

J Wang; PA Gleeson; L Fourriere

Journal article

Spatial–Temporal Mapping Reveals the Golgi as the Major Processing Site for the Pathogenic Swedish APP Mutation: Familial APP Mutant Shifts the Major APP Processing Site

J Wang, PA Gleeson, L Fourriere

Traffic | WILEY | Published : 2024

DOI: 10.1111/tra.12932

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Abstract

Alzheimer's disease is associated with increased levels of amyloid beta (Aβ) generated by sequential intracellular cleavage of amyloid precursor protein (APP) by membrane-bound secretases. However, the spatial and temporal APP cleavage events along the trafficking pathways are poorly defined. Here, we use the Retention Using Selective Hooks (RUSH) to compare in real time the anterograde trafficking and temporal cleavage events of wild-type APP (APPwt) with the pathogenic Swedish APP (APPswe) and the disease-protective Icelandic APP (APPice). The analyses revealed differences in the trafficking profiles and processing between APPwt and the APP familial mutations. While APPwt was predominantly..

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University of Melbourne Researchers

Paul Gleeson Author

Lou Fourriere-Chea Author

Related Projects (1)

DEFINING THE ANTEROGRADE AND ENDOCYTIC TRAFFICKING PATHWAYS IN PRIMARY NEURONS; RELEVANCE TO DYSFUNCTIONAL TRAFFICKING OF BACE1 AND APP IN ALZHEIMER’S DISEASE

Alzheimer’s disease results from toxic peptides arising from the cleavage of a large molecule called APP in the brain. The production of tox..

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Funding Acknowledgements

Microscopy and image processing were performed at the Biological Optical Microscopy Platform (BOMP), and the Biosciences Microscopy Unit, at the University of Melbourne. This work was supported by funding from the National Health and Medical Research Council of Australia (APP1163862: 2013344). J.W. is supported by a University of Melbourne International Postgraduate Award. We acknowledge Ellie Cho for her expertise in cell quantification, Fiona Houghton for excellent laboratory support and Dr Wei Hong Toh for the APP-mCherry construct. Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians.