Dataset Information

Cross-Beta Helical Fibrils of Tau and TMEM106B in Gray and White Matter of Multiple System Tauopathy with Presenile Dementia

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Amber Mosley Ruben Vidal

PROVIDER: MSV000090845 | MassIVE | Tue Dec 06 10:08:00 GMT 2022

SECONDARY ACCESSION(S): PXD038588

REPOSITORIES: MassIVE

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Cross-β helical filaments of Tau and TMEM106B in gray and white matter of multiple system tauopathy with presenile dementia.

Hoq Md Rejaul MR Bharath Sakshibeedu R SR Hallinan Grace I GI Fernandez Anllely A Vago Frank S FS Ozcan Kadir A KA Li Daoyi D Garringer Holly J HJ Vidal Ruben R Ghetti Bernardino B Jiang Wen W

Acta neuropathologica 20230323 5

PMID: 36952000

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