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PXD018855 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTau molecular diversity mediates clinical heterogeneity in Alzheimer’s disease
DescriptionAlzheimer’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.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPieter Beerepoot
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-04-28 06:49:19ID requested
12020-06-17 07:50:32announced
22020-08-09 22:51:56announced2020-08-10: Updated publication reference for PubMed record(s): 32572268.
Publication List
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]
Keyword List
submitter keyword: Human, Brain, QExactive
Contact List
Judith Steen
contact affiliationF.M Kirby Neurobiology Center, Boston Children’s Hospital, Boston, MA, USA. Harvard Medical School, Boston, MA, USA
contact emailjudith.steen@childrens.harvard.edu
lab head
Pieter Beerepoot
contact affiliationBoston Children's Hospital
contact emailpieter.beerepoot@childrens.harvard.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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