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PXD017916

PXD017916 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCompare the SDS-insoluble proteins among 7 Amyloidosis mouse models
DescriptionA hallmark pathology of Alzheimer’s disease (AD) is the formation of amyloid ß (Aß) deposits that exhibit diverse localization and morphologies, ranging from diffuse to cored-neuritic deposits in brain parenchyma, with cerebral vascular deposition in leptomeningeal and parenchymal compartments. Most AD brains exhibit the full spectrum of pathologic Aß morphologies. In the course of studies to model AD amyloidosis, we have generated multiple transgenic mouse models that vary in the nature of the transgene constructs that are expressed; including the species origin of Aß peptides, the levels and length of Aß that is deposited, and whether mutant presenilin 1 (PS1) is co-expressed. These models recapitulate features of human AD amyloidosis, but interestingly some models can produce pathology in which one type of Aß morphology dominates. In prior studies of mice that primarily develop cored-neuritic deposits, we determined that Aß deposition is associated with changes in cytosolic protein solubility in which a subset of proteins become detergent-insoluble, indicative of secondary proteome instability. Here, we survey changes in cytosolic protein solubility across seven different transgenic mouse models that exhibit a range of Aß deposit morphologies. We find a surprisingly diverse range of changes in proteome solubility across these models. Mice that deposit human Aß40 and Aß42 in cored-neuritic plaques had the most robust changes in proteome solubility. Insoluble cytosolic proteins were also detected in the brains of mice that develop diffuse Aß42 deposits but to a lesser extent. Notably, mice with cored deposits containing only Aß42 had relatively few proteins that became detergent-insoluble. Our data provide new insight into the diversity of biological effects that can be attributed to different types of Aß pathology and support the view that fibrillar cored-neuritic plaque pathology is the more disruptive Aß pathology in the Alzheimer’s cascade.
HostingRepositoryPRIDE
AnnounceDate2020-04-15
AnnouncementXMLSubmission_2020-04-15_05:27:55.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGuilian Xu
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListubiquitination signature dipeptidyl lysine; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-03-05 23:32:13ID requested
12020-04-15 05:27:56announced
Publication List
Xu G, Fromholt SE, Chakrabarty P, Zhu F, Liu X, Pace MC, Koh J, Golde TE, Levites Y, Lewis J, Borchelt DR, amyloidosis. Acta Neuropathol Commun, 8(1):43(2020) [pubmed]
Keyword List
submitter keyword: transgenic mice, Alzheimer's disease, amyloid, protein homoestasis, detergent-insoluble proteins
Contact List
David R. Borchelt
contact affiliationDepartment of Neurscience, College of Medicine, University of Florida
contact emaildrb1@ufl.edu
lab head
Guilian Xu
contact affiliationDepartment of Neurscience, College of Medicine, University of Florida
contact emailxugl@ufl.edu
dataset submitter
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Dataset FTP location
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