PXD006552

PXD006552 is an original dataset announced via ProteomeXchange.

Title	Diversity of Amyloid-beta Proteoforms in the Alzheimer's Disease Brain
Description	Amyloid-beta (Aβ) plays a key role in the pathogenesis of Alzheimer’s disease (AD), but little is known about the proteoforms present in human AD brain. We used high-resolution mass spectrometry to analyze intact, undigested Aβ from purified soluble aggregates and insoluble material in brains of 6 cases with severe dementia and pathologically confirmed AD. The soluble aggregates are especially relevant because they are believed to be the most toxic form of Aβ. We found a diversity of Aβ peptides, with 26 unique proteoforms including various N- and C-terminal truncations. N- and C-terminal truncations comprised 73% and 30%, respectively, of the number of Aβ proteoforms detected. The Aβ proteoforms segregated between the soluble and more insoluble aggregates with N-terminal truncations predominating in the insoluble material and C- terminal truncations segregating into the soluble aggregates. In contrast, canonical Aβ comprised the minority of the number of identified proteoforms (15.3%) and did not distinguish between the soluble and more insoluble aggregates. The relative abundance of many truncated Aβ proteoforms did not correlate with post-mortem interval, suggesting they are not artefacts. This heterogeneity of Aβ proteoforms deepens our understanding of AD and offers many new avenues for investigation into pathological mechanisms of the disease, with implications for therapeutic development.
HostingRepository	PRIDE
AnnounceDate	2017-08-28
AnnouncementXML	Submission_2017-08-28_08:08:55.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD006552
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Norelle Wildburger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Ethyl; Amidated; Methyl; Formyl; Oxidation; Carbamidomethyl; Glycosyl; Carboxy; Pyridylethyl; Trioxidation; Cation:Na; Glu->pyro-Glu; Deamidated; Ammonium; Dehydrated; Dimethyl; Acetyl; Sulfo
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-05-19 08:29:13	ID requested
⏵ 1	2017-08-28 08:08:57	announced

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]

curator keyword: Biomedical

submitter keyword: Alzheimer’s disease, top-down mass spectrometry, amyloid-beta, proteoforms, post-translational modifications (PTMs), truncations

David L. Brody
contact affiliation	Washington University School of Medicine Department of Neurology
contact email	brodyd@wustl.edu
lab head
Norelle Wildburger
contact affiliation	Department of Neurology
contact email	wildburger@msn.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006552
     1. Label: PRIDE project
     2. Name: Diversity of Amyloid-beta Proteoforms in the Alzheimer's Disease Brain