PXD017916

PXD017916 is an original dataset announced via ProteomeXchange.

Title	Compare the SDS-insoluble proteins among 7 Amyloidosis mouse models
Description	A 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.
HostingRepository	PRIDE
AnnounceDate	2020-04-15
AnnouncementXML	Submission_2020-04-15_05:27:55.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guilian Xu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	ubiquitination signature dipeptidyl lysine; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-05 23:32:13	ID requested
⏵ 1	2020-04-15 05:27:56	announced

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]

submitter keyword: transgenic mice, Alzheimer's disease, amyloid, protein homoestasis, detergent-insoluble proteins

David R. Borchelt
contact affiliation	Department of Neurscience, College of Medicine, University of Florida
contact email	drb1@ufl.edu
lab head
Guilian Xu
contact affiliation	Department of Neurscience, College of Medicine, University of Florida
contact email	xugl@ufl.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017916
     1. Label: PRIDE project
     2. Name: Compare the SDS-insoluble proteins among 7 Amyloidosis mouse models