PXD005119 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Extraordinary Diversity of Amyloid-beta Proteoforms in Human Alzheimer's Disease Brain |
Description | Amyloid-beta (Aβ) plays a key role in the neuropathogenesis of Alzheimer’s disease, but little is known about the proteoforms (i.e., all protein variants of a single gene including post-translational modifications and sequence variants) present in human AD brain. We used high-resolution mass spectrometry to analyze intact, whole Aβ from soluble and insoluble aggregates in brains of 6 cases with severe dementia and pathologically confirmed Alzheimer’s disease. We found an extraordinary diversity of Aβ peptides totaling 91 unique proteoforms including various N- and C-terminal truncations, 17 different types of post-translational modifications (PTMs), and remarkably 5 amino acid variants in the peptide sequence never before described. Ratios of Aβ proteoforms did not distinguish between soluble and insoluble aggregates, but four individual Aβ proteoforms, three in the insoluble and one in the soluble fraction, were markedly increased when compared across aggregates. Such heterogeneity of the Aβ peptide both deepens our understanding of AD, but perhaps also warrants pause and consideration in our investigation into pathological mechanisms of the disease and therapeutic development. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:32:52.915.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Norelle Wildburger |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2016-10-10 01:44:32 | ID requested | |
1 | 2017-09-04 00:36:46 | announced | |
⏵ 2 | 2024-10-22 04:32:53 | announced | 2024-10-22: Updated project metadata. |
Publication List
Wildburger NC, Esparza TJ, LeDuc RD, Fellers RT, Thomas PM, Cairns NJ, Kelleher NL, Bateman RJ, Brody DL, Diversity of Amyloid-beta Proteoforms in the Alzheimer's Disease Brain. Sci Rep, 7(1):9520(2017) [pubmed] |
10.1038/s41598-017-10422-x; |
Keyword List
curator keyword: Biomedical |
submitter keyword: Human AD Brain |
nLC-MS/MS |
Contact List
David Brody |
contact affiliation | Professor of Neuology Washington University School of Medicine St. Louis, MO 61130 |
contact email | brodyd@wustl.edu |
lab head | |
Norelle Wildburger |
contact affiliation | Washington University |
contact email | n.wildburger@wustl.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD005119
- Label: PRIDE project
- Name: Extraordinary Diversity of Amyloid-beta Proteoforms in Human Alzheimer's Disease Brain