PXD018855

PXD018855 is an original dataset announced via ProteomeXchange.

Title	Tau molecular diversity mediates clinical heterogeneity in Alzheimer’s disease
Description	Alzheimer’s disease (AD) causes unrelenting, progressive cognitive impairments, but its course is heterogeneous, with a broad range of rates of cognitive decline. The spread of tau aggregates (neurofibrillary tangles) across the cerebral cortex parallels symptom severity. We hypothesized that the kinetics of tau spread may vary if the properties of the propagating tau proteins varied across individuals. We carried out biochemical, biophysical, and both cell- and animal-based bioactivity assays, and mass spectrometry, to characterize tau in 32 AD patients. We found striking patient-to-patient heterogeneity in the hyperphosphorylated species of soluble, oligomeric, seed-competent tau. Tau seeding activity correlates with the aggressiveness of the clinical disease, and some post-translational modification sites appear to be associated with both enhanced seeding activity and worse clinical outcomes, while others are not. These data suggest that different individuals with “typical” AD may have distinct biochemical features of tau. These data are consistent with the possibility that individuals with AD, much like cancer patients, may have multiple molecular drivers of an otherwise common phenotype, and emphasizes the potential for personalized therapeutic approaches for slowing clinical progression in AD.
HostingRepository	PRIDE
AnnounceDate	2020-08-09
AnnouncementXML	Submission_2020-08-09_22:51:55.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pieter Beerepoot
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-28 06:49:19	ID requested
1	2020-06-17 07:50:32	announced
⏵ 2	2020-08-09 22:51:56	announced	2020-08-10: Updated publication reference for PubMed record(s): 32572268.

Dujardin S, Commins C, Lathuiliere A, Beerepoot P, Fernandes AR, Kamath TV, De Los Santos MB, Klickstein N, Corjuc DL, Corjuc BT, Dooley PM, Viode A, Oakley DH, Moore BD, Mullin K, Jean-Gilles D, Clark R, Atchison K, Moore R, Chibnik LB, Tanzi RE, Frosch MP, Serrano-Pozo A, Elwood F, Steen JA, Kennedy ME, Hyman BT, Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease. Nat Med, 26(8):1256-1263(2020) [pubmed]

submitter keyword: Human, Brain, QExactive

Judith Steen
contact affiliation	F.M Kirby Neurobiology Center, Boston Children’s Hospital, Boston, MA, USA. Harvard Medical School, Boston, MA, USA
contact email	judith.steen@childrens.harvard.edu
lab head
Pieter Beerepoot
contact affiliation	Boston Children's Hospital
contact email	pieter.beerepoot@childrens.harvard.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/2020/08/PXD018855

PRIDE project URI

• PRIDE
  1. PXD018855
     1. Label: PRIDE project
     2. Name: Tau molecular diversity mediates clinical heterogeneity in Alzheimer’s disease