PXD018855 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2020-06-17 |
AnnouncementXML | Submission_2020-06-17_07:50:32.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 |
Dataset History
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. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Human, Brain, QExactive |
Contact List
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 | |
Full Dataset Link List
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/2020/06/PXD018855 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD018855
- Label: PRIDE project
- Name: Tau molecular diversity mediates clinical heterogeneity in Alzheimer’s disease