PXD038588

PXD038588 is an original dataset announced via ProteomeXchange.

Title	Cross-Beta Helical Fibrils of Tau and TMEM106B in Gray and White Matter of Multiple System Tauopathy with Presenile Dementia
Description	Neurodegenerative diseases characterized by tau aggregates have distinct tau pathological profiles that may differ in relation to the morphology and structure of the filaments, the tau-isoform composition and the cell types and brain areas that are affected. Neurons, dendrites and axonal terminals are situated in the gray matter, whereas axonal tracts and oligodendrocytes are prominent in the white matter. Whilst astrocytes and other glial cells are found throughout both gray and white matter, oligodendrocytes are preferentially located in the white matter, where their role is to myelinate axonal nerve fibers. Recently, the atomic structures of tau filaments isolated from samples from gray matter, which contains predominantly neuronal tau, have been characterized. Whether glial tau fibrils share a common fold with neuronal tau fibrils in the same disease remains unknown. Using cryogenic electron microscopy (cryo-EM), we determined for the first time the structure of tau filaments from gray and white matter. We isolated tau post-mortem from the brain of two individuals with multiple system tauopathy with presenile dementia (MSTD) caused by the +3 mutation in MAPT and determined that they have identical structures (the AGD type 2 fold). In addition, we identified and determined the structure of TMEM106B in gray and white matter regions of the brain of the same individuals. Our findings support the notion that in the same disease there is not a region/cell type-specific form of tau or TMEM106B, and that a similar mechanism of fibrillization and/or transmission in neuronal and glial cell types may exist. Whether TMEM106B fibrils represent a true age or disease related process remains to be fully determined.
HostingRepository	MassIVE
AnnounceDate	2024-06-12
AnnouncementXML	Submission_2024-06-12_08:03:14.750.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Emma Doud
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Phospho
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-06 10:08:20	ID requested
⏵ 1	2024-06-12 08:03:15	announced

Hoq MR, Bharath SR, Hallinan GI, Fernandez A, Vago FS, Ozcan KA, Li D, Garringer HJ, Vidal R, Ghetti B, Jiang W, helical filaments of Tau and TMEM106B in gray and white matter of multiple system tauopathy with presenile dementia. Acta Neuropathol, 145(5):707-710(2023) [pubmed]

submitter keyword: tau, TMEM106b, Cryo-EM, neurodegeneration

Ruben Vidal
contact affiliation	Indiana University School of Medicine
contact email	rvidal@iupui.edu
lab head
Amber Mosley
contact affiliation	Indiana University School of Medicine
contact email	almosley@iu.edu
lab head
Emma Doud
contact affiliation	IUSM
contact email	edoud@iu.edu
dataset submitter

MassIVE dataset URI

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