PXD025663

PXD025663 is an original dataset announced via ProteomeXchange.

Title	Structure of Tau filaments in Prion protein amyloidoses
Description	In human neurodegenerative diseases associated with the intracellular aggregation of Tau protein, the ordered cores of Tau filaments adopt distinct folds. Here, we analyze Tau filaments isolated from the brain of individuals affected by Prion-Protein cerebral amyloid angiopathy (PrP-CAA) and Gerstmann-Sträussler-Scheinker (GSS) disease, two genetically determined Prion protein (PrP) amyloidoses characterized by the deposition of PrP amyloid (APrP) in the vessel walls and in the cerebral parenchyma, respectively. A nonsense and a missense mutation in the PRNP gene lead to a premature termination of translation at codon position 160 (Q160Ter) of PrP in PrP-CAA, or to the substitution of an amino acid at residue 198 (F198S) of PrP in GSS. These two diseases have different clinical and pathologic phenotypes; however, in both diseases, neuropathologic analyses have consistently shown the presence of numerous neurofibrillary tangles (NFTs) made of filamentous Tau aggregates in neurons. We report that Tau filaments in PrP-CAA and GSS are composed of 3-repeat and 4-repeat Tau isoforms, having a striking similarity to NFTs in Alzheimer disease (AD). In PrP-CAA, Tau filaments are made of both paired helical filaments (PHFs) and straight filaments (SFs), while in GSS only PHFs were found. Mass spectrometry analyses of Tau filaments extracted from PrP-CAA and GSS brains show the presence of post-translational modifications that are comparable to those seen in Tau aggregates from AD. Cryo-EM analysis reveals that the atomic models of the Tau filaments obtained from PrP-CAA and GSS are identical to those of the Tau filaments from AD, and are therefore distinct from those of Pick disease, chronic traumatic encephalopathy, and corticobasal degeneration. Our data support the hypothesis that in the presence of amyloid deposits and regardless of the primary amino acid sequence of the amyloid protein, similar molecular mechanisms are at play in the formation of identical Tau filaments.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_03:02:20.281.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD025663
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Emma Doud
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine; phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-27 08:33:51	ID requested
⏵ 1	2022-02-17 03:02:21	announced

Hallinan GI, Hoq MR, Ghosh M, Vago FS, Fernandez A, Garringer HJ, Vidal R, Jiang W, Ghetti B, Structure of Tau filaments in Prion protein amyloidoses. Acta Neuropathol, 142(2):227-241(2021) [pubmed]

submitter keyword: Brain, GSS, PrP-CAA, Tau, APrP, Cryo-EM, seeding, neurodegeneration

Ruben Vidal
contact affiliation	Dept. of Pathology and Laboratory Medicine, Indiana University School of Medicine, 635 Barnhill Dr., MSB A136, Indianapolis, IN 46202
contact email	rvidal@iupui.edu
lab head
Emma Doud
contact affiliation	Indiana University School of Medicine
contact email	edoud@iu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025663
     1. Label: PRIDE project
     2. Name: Structure of Tau filaments in Prion protein amyloidoses