PXD005119

PXD005119 is an original dataset announced via ProteomeXchange.

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

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.

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;

curator keyword: Biomedical

submitter keyword: Human AD Brain

nLC-MS/MS

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/09/PXD005119

PRIDE project URI

• PRIDE
  1. PXD005119
     1. Label: PRIDE project
     2. Name: Extraordinary Diversity of Amyloid-beta Proteoforms in Human Alzheimer's Disease Brain