Specific post-translational modifications of soluble tau protein distinguishes Alzheimer's disease and primary tauopathies.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 06 2023
22 06 2023
Historique:
received:
05
12
2022
accepted:
07
06
2023
medline:
26
6
2023
pubmed:
23
6
2023
entrez:
22
6
2023
Statut:
epublish
Résumé
Tau protein aggregates in several neurodegenerative disorders, referred to as tauopathies. The tau isoforms observed in post mortem human brain aggregates is used to classify tauopathies. However, distinguishing tauopathies ante mortem remains challenging, potentially due to differences between insoluble tau in aggregates and soluble tau in body fluids. Here, we demonstrated that tau isoforms differ between tauopathies in insoluble aggregates, but not in soluble brain extracts. We therefore characterized post-translational modifications of both the aggregated and the soluble tau protein obtained from post mortem human brain tissue of patients with Alzheimer's disease, cortico-basal degeneration, Pick's disease, and frontotemporal lobe degeneration. We found specific soluble signatures for each tauopathy and its specific aggregated tau isoforms: including ubiquitination on Lysine 369 for cortico-basal degeneration and acetylation on Lysine 311 for Pick's disease. These findings provide potential targets for future development of fluid-based biomarker assays able to distinguish tauopathies in vivo.
Identifiants
pubmed: 37349319
doi: 10.1038/s41467-023-39328-1
pii: 10.1038/s41467-023-39328-1
pmc: PMC10287718
doi:
Substances chimiques
tau Proteins
0
Lysine
K3Z4F929H6
Protein Isoforms
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3706Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023. The Author(s).
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