Journal Article

DZNE-2020-03559

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Extracellular monomeric tau protein is sufficient to initiate the spread of tau protein pathology.

Michel, C. H. ; Kumar, S.DZNE* ; Pinotsi, D. ; Tunnacliffe, A. ; St George-Hyslop, P. ; Mandelkow, E.DZNE* ; Mandelkow, E.-M.DZNE* ; Kaminski, C. F. (Corresponding author) ; Kaminski Schierle, G. S.

2014
Soc.60645 Bethesda, Md.

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Please use a persistent id in citations: doi:10.1074/jbc.M113.515445

Abstract: Understanding the formation and propagation of aggregates of the Alzheimer disease-associated Tau protein in vivo is vital for the development of therapeutics for this devastating disorder. Using our recently developed live-cell aggregation sensor in neuron-like cells, we demonstrate that different variants of exogenous monomeric Tau, namely full-length Tau (hTau40) and the Tau-derived construct K18 comprising the repeat domain, initially accumulate in endosomal compartments, where they form fibrillar seeds that subsequently induce the aggregation of endogenous Tau. Using superresolution imaging, we confirm that fibrils consisting of endogenous and exogenous Tau are released from cells and demonstrate their potential to spread Tau pathology. Our data indicate a greater pathological risk and potential toxicity than hitherto suspected for extracellular soluble Tau.

Keyword(s): Animals (MeSH) ; Blotting, Western (MeSH) ; Cell Line (MeSH) ; Cell Line, Tumor (MeSH) ; Endocytosis (MeSH) ; Endosomes: metabolism (MeSH) ; Exocytosis (MeSH) ; Extracellular Space: metabolism (MeSH) ; Humans (MeSH) ; Lysosomes: metabolism (MeSH) ; Microscopy, Confocal (MeSH) ; Microscopy, Electron (MeSH) ; Models, Biological (MeSH) ; Neurofibrillary Tangles: metabolism (MeSH) ; Neurofibrillary Tangles: ultrastructure (MeSH) ; Neurons: metabolism (MeSH) ; Neurons: pathology (MeSH) ; Tauopathies: metabolism (MeSH) ; Transport Vesicles: metabolism (MeSH) ; tau Proteins: metabolism (MeSH) ; tau Proteins

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Contributing Institute(s):

1. Structural Principles of Neurodegeneration (AG Mandelkow 1)
2. Cell and Animal Models of Neurodegeneration (AG Mandelkow 2)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2014

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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