Mutation ∆K281 in MAPT causes Pick's disease.

Electron cryo-microscopy FTDP-17T Luminescent conjugated oligothiophenes MAPT mutation ∆K281 Pick’s disease Silver staining Tau

Journal

Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041

Informations de publication

Date de publication:
08 2023
Historique:
received: 17 05 2023
accepted: 08 06 2023
revised: 08 06 2023
medline: 10 7 2023
pubmed: 23 6 2023
entrez: 23 6 2023
Statut: ppublish

Résumé

Two siblings with deletion mutation ∆K281 in MAPT developed frontotemporal dementia. At autopsy, numerous inclusions of hyperphosphorylated 3R Tau were present in neurons and glial cells of neocortex and some subcortical regions, including hippocampus, caudate/putamen and globus pallidus. The inclusions were argyrophilic with Bodian silver, but not with Gallyas-Braak silver. They were not labelled by an antibody specific for tau phosphorylated at S262 and/or S356. The inclusions were stained by luminescent conjugated oligothiophene HS-84, but not by bTVBT4. Electron cryo-microscopy revealed that the core of tau filaments was made of residues K254-F378 of 3R Tau and was indistinguishable from that of Pick's disease. We conclude that MAPT mutation ∆K281 causes Pick's disease.

Identifiants

pubmed: 37351604
doi: 10.1007/s00401-023-02598-6
pii: 10.1007/s00401-023-02598-6
pmc: PMC10329087
doi:

Substances chimiques

Silver 3M4G523W1G
tau Proteins 0
MAPT protein, human 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

211-226

Subventions

Organisme : Medical Research Council
ID : MC_UP_A025-1013
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG080001
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072976
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS110437
Pays : United States
Organisme : Medical Research Council
ID : MC_U105184291
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG010133
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

Manuel Schweighauser (M)

Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.

Holly J Garringer (HJ)

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.

Therése Klingstedt (T)

Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Department of Physics, Chemistry and Biology, Lingköping University, Lingköping, Sweden.

K Peter R Nilsson (KPR)

Department of Physics, Chemistry and Biology, Lingköping University, Lingköping, Sweden.

Masami Masuda-Suzukake (M)

Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Department of Brain and Neuroscience, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

Jill R Murrell (JR)

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Pathology and Laboratory Medicine, Children's Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Shannon L Risacher (SL)

Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.

Ruben Vidal (R)

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.

Sjors H W Scheres (SHW)

Medical Research Council Laboratory of Molecular Biology, Cambridge, UK. scheres@mrc-lmb.cam.ac.uk.

Michel Goedert (M)

Medical Research Council Laboratory of Molecular Biology, Cambridge, UK. mg@mrc-lmb.cam.ac.uk.

Bernardino Ghetti (B)

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. bghetti@iupui.edu.

Kathy L Newell (KL)

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. klnewell@iu.edu.

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