A New family with frontotemporal dementia with intronic 10+3 splice site mutation in the tau gene:: neuropathology and molecular effects

Publikationstyp:

Zeitschriftenaufsatz

Metadaten:

Autoren

M Neumann
M Mittelbronn
P Simon
B Vanmassenhove
R de Silva
A Lees
J Klapp
R Meyermann
HA Kretzschmar

Autoren-URL

https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000231015400003&DestLinkType=FullRecord&DestApp=WOS_CPL

DOI

10.1111/j.1365-2990.2005.00629.x

Externe Identifier

Clarivate Analytics Document Solution ID: 952OM
PubMed Identifier: 16008820

ISSN

0305-1846

Ausgabe der Veröffentlichung

Zeitschrift

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

Schlüsselwörter

alternative splicing
frontotemporal dementia
FTDP-17
tauopathy

Paginierung

362 - 373

Datum der Veröffentlichung

2005

Status

Published

Titel

A New family with frontotemporal dementia with intronic 10+3 splice site mutation in the <i>tau</i> gene:: neuropathology and molecular effects

Sub types

Article

Ausgabe der Zeitschrift

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:

Abstract

Mutations in the tau gene cause familial frontotemporal dementia with parkinsonism linked to chromosome 17 characterized by filamentous tau protein deposits. Here we describe the clinical and neuropathological features of a case from a newly identified family with an intron 10+3‐splice site mutation in the tau gene. The proband presented with severe personality changes and stereotyped speech followed by parkinsonian symptoms. He died at age 56 after a disease duration of approximately 6 years. At autopsy, there was marked frontotemporal degeneration with abundant tau‐immunoreactive neuronal and glial inclusions widespread in the cortex and brainstem. RT‐PCR analysis revealed a 3.7‐fold increase of tau transcripts with exon 10, resulting in an 1.7‐fold higher expression level of 4‐repeat tau isoforms in soluble tau fractions when compared to control brains and exclusively 4‐repeat tau isoforms in the sarcosyl‐insoluble tau fractions. In accordance with the hypothesis that the overexpression leads to saturation of microtubule binding sites and an increase of unbound 4‐repeat tau isoforms which assemble into filaments, the neuronal and glial inclusions in this case were exclusively composed of 4‐repeat tau isoforms. The clinical and neuropathological data of this family are compared with results from the two other published families with the intron 10 + 3 mutation, the MSTD and the SOT 254 family.

Autoren

M Neumann
M Mittelbronn
P Simon
B Vanmassenhove
R De Silva
A Lees
J Klapp
R Meyermann
HA Kretzschmar

DOI

10.1111/j.1365-2990.2005.00629.x

eISSN

1365-2990

ISSN

0305-1846

Ausgabe der Veröffentlichung

Zeitschrift

Neuropathology and Applied Neurobiology

Sprache

Online publication date

2005

Paginierung

362 - 373

Datum der Veröffentlichung

2005

Status

Published

Herausgeber

Wiley

Herausgeber URL

http://dx.doi.org/10.1111/j.1365-2990.2005.00629.x

Datum der Datenerfassung

2023

Titel

A New family with frontotemporal dementia with intronic 10+3 splice site mutation in the <i>tau</i> gene: neuropathology and molecular effects

Ausgabe der Zeitschrift

Datenquelle: Crossref

Abstract

Mutations in the tau gene cause familial frontotemporal dementia with parkinsonism linked to chromosome 17 characterized by filamentous tau protein deposits. Here we describe the clinical and neuropathological features of a case from a newly identified family with an intron 10+3-splice site mutation in the tau gene. The proband presented with severe personality changes and stereotyped speech followed by parkinsonian symptoms. He died at age 56 after a disease duration of approximately 6 years. At autopsy, there was marked frontotemporal degeneration with abundant tau-immunoreactive neuronal and glial inclusions widespread in the cortex and brainstem. RT-PCR analysis revealed a 3.7-fold increase of tau transcripts with exon 10, resulting in an 1.7-fold higher expression level of 4-repeat tau isoforms in soluble tau fractions when compared to control brains and exclusively 4-repeat tau isoforms in the sarcosyl-insoluble tau fractions. In accordance with the hypothesis that the overexpression leads to saturation of microtubule binding sites and an increase of unbound 4-repeat tau isoforms which assemble into filaments, the neuronal and glial inclusions in this case were exclusively composed of 4-repeat tau isoforms. The clinical and neuropathological data of this family are compared with results from the two other published families with the intron 10 + 3 mutation, the MSTD and the SOT 254 family.

Addresses

Center for Neuropathology and Prion Research, Ludwig-Maximilians University, München, Germany.

Autoren

M Neumann
M Mittelbronn
P Simon
B Vanmassenhove
R de Silva
A Lees
J Klapp
R Meyermann
HA Kretzschmar

DOI

10.1111/j.1365-2990.2005.00629.x

eISSN

1365-2990

Externe Identifier

PubMed Identifier: 16008820

Open access

false

ISSN

0305-1846

Ausgabe der Veröffentlichung

Zeitschrift

Neuropathology and applied neurobiology

Schlüsselwörter

Brain
Humans
Dementia
tau Proteins
Protein Isoforms
RNA Splice Sites
Immunoblotting
Immunohistochemistry
Reverse Transcriptase Polymerase Chain Reaction
Pedigree
DNA Mutational Analysis
Base Sequence
Mutation
Middle Aged
Female
Male

Sprache

eng

Medium

Paginierung

362 - 373

Datum der Veröffentlichung

2005

Status

Published

Datum der Datenerfassung

2005

Titel

A new family with frontotemporal dementia with intronic 10+3 splice site mutation in the tau gene: neuropathology and molecular effects.

Sub types

Comparative Study
Research Support, Non-U.S. Gov't
Journal Article
Case Reports

Ausgabe der Zeitschrift

Datenquelle: Europe PubMed Central

Abstract

Mutations in the tau gene cause familial frontotemporal dementia with parkinsonism linked to chromosome 17 characterized by filamentous tau protein deposits. Here we describe the clinical and neuropathological features of a case from a newly identified family with an intron 10+3-splice site mutation in the tau gene. The proband presented with severe personality changes and stereotyped speech followed by parkinsonian symptoms. He died at age 56 after a disease duration of approximately 6 years. At autopsy, there was marked frontotemporal degeneration with abundant tau-immunoreactive neuronal and glial inclusions widespread in the cortex and brainstem. RT-PCR analysis revealed a 3.7-fold increase of tau transcripts with exon 10, resulting in an 1.7-fold higher expression level of 4-repeat tau isoforms in soluble tau fractions when compared to control brains and exclusively 4-repeat tau isoforms in the sarcosyl-insoluble tau fractions. In accordance with the hypothesis that the overexpression leads to saturation of microtubule binding sites and an increase of unbound 4-repeat tau isoforms which assemble into filaments, the neuronal and glial inclusions in this case were exclusively composed of 4-repeat tau isoforms. The clinical and neuropathological data of this family are compared with results from the two other published families with the intron 10 + 3 mutation, the MSTD and the SOT 254 family.

Autoren

M Neumann
M Mittelbronn
P Simon
B Vanmassenhove
R de Silva
A Lees
J Klapp
R Meyermann
HA Kretzschmar

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/16008820

DOI

10.1111/j.1365-2990.2005.00629.x

ISSN

0305-1846

Ausgabe der Veröffentlichung

Zeitschrift

Neuropathol Appl Neurobiol

Schlüsselwörter

Base Sequence
Brain
DNA Mutational Analysis
Dementia
Female
Humans
Immunoblotting
Immunohistochemistry
Male
Middle Aged
Mutation
Pedigree
Protein Isoforms
RNA Splice Sites
Reverse Transcriptase Polymerase Chain Reaction
tau Proteins

Sprache

eng

Country

England

Paginierung

362 - 373

PII

NAN629

Datum der Veröffentlichung

2005

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2005

Titel

A new family with frontotemporal dementia with intronic 10+3 splice site mutation in the tau gene: neuropathology and molecular effects.

Sub types

Case Reports
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

Datenquelle: PubMed

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A New family with frontotemporal dementia with intronic 10+3 splice site mutation in the tau gene:: neuropathology and molecular effects

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