PXD025668-2

PXD025668 is an original dataset announced via ProteomeXchange.

Title	Alzheimer's Disease Isomerization
Description	Amino acid isomerization is a spontaneous chemical modification potentially related to the underlying causes of Alzheimer’s disease (AD). We demonstrate that data-independent acquisition mass spectrometry can be used to characterize isomerization in complex protein mixtures. Examination of a large cohort of brain samples revealed a striking relationship between isomerization of tau and AD status. Surprisingly, isomerization was found to be more abundant in both autosomal dominant and sporadic AD samples relative to controls. We hypothesize that lower autophagic flux in AD brains accounts for these results. Additional data strongly support this hypothesis, including quantitative analysis of proteins related to autophagy. For example, isomerization of tau is positively correlated with levels of p62, a recognized indicator of autophagic inhibition. In sum, the data suggest strong ties between isomerization and autophagic flux, which may therefore represent a promising target for future investigations into the therapy and prevention of AD.
HostingRepository	PanoramaPublic
AnnounceDate	2022-03-16
AnnouncementXML	Submission_2022-03-16_12:46:22.692.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Gennifer Merrihew
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Deamidated; Carbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-27 12:45:30	ID requested
1	2021-11-12 08:22:51	announced
⏵ 2	2022-03-16 12:46:23	announced	: Added publication

Hubbard EE, Heil LR, Merrihew GE, Chhatwal JP, Farlow MR, McLean CA, Ghetti B, Newell KL, Frosch MP, Bateman RJ, Larson EB, Keene CD, Perrin RJ, Montine TJ, MacCoss MJ, Julian RR, Does Data-Independent Acquisition Data Contain Hidden Gems? A Case Study Related to Alzheimer's Disease. J Proteome Res, 21(1):118-131(2022) [pubmed]

submitter keyword: amino acid isomerization, Alzheimer’s disease, autophagy, DIA mass spectrometry

Michael MacCoss
contact affiliation	University of Washington
contact email	maccoss@uw.edu
lab head
Gennifer Merrihew
contact affiliation	University of Washington
contact email	genn@uw.edu
dataset submitter

Panorama Public dataset URI