Clinical heterogeneity of frontotemporal dementia and Parkinsonism linked to chromosome 17 caused by MAPT N279K mutation in relation to tau positron emission tomography features.
MAPT
N279K mutation
frontotemporal dementia
tau PET
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
14
06
2018
revised:
08
12
2018
accepted:
02
01
2019
pubmed:
19
2
2019
medline:
10
1
2020
entrez:
19
2
2019
Statut:
ppublish
Résumé
While mechanistic links between tau abnormalities and neurodegeneration have been proven in frontotemporal dementia and parkinsonism linked to chromosome 17 caused by MAPT mutations, variability of the tau pathogenesis and its relation to clinical progressions in the same MAPT mutation carriers are yet to be clarified. The present study aimed to analyze clinical profiles, tau accumulations, and their correlations in 3 kindreds with frontotemporal dementia and parkinsonism linked to chromosome 17 attributed to the MAPT N279K mutation. Four patients with N279K mutant frontotemporal dementia and parkinsonism linked to chromosome 17/MAPT underwent [ Haplotype assays revealed that these kindreds originated from a single founder. Despite homogeneity of the disease-causing MAPT allele, clinical progression was more rapid in 2 kindreds than in the other. The kindred with slow progression showed mild tau depositions, mostly confined to the midbrain and medial temporal areas. In contrast, kindreds with rapid progression showed profoundly increased [ [
Sections du résumé
BACKGROUND
While mechanistic links between tau abnormalities and neurodegeneration have been proven in frontotemporal dementia and parkinsonism linked to chromosome 17 caused by MAPT mutations, variability of the tau pathogenesis and its relation to clinical progressions in the same MAPT mutation carriers are yet to be clarified.
OBJECTIVES
The present study aimed to analyze clinical profiles, tau accumulations, and their correlations in 3 kindreds with frontotemporal dementia and parkinsonism linked to chromosome 17 attributed to the MAPT N279K mutation.
METHODS
Four patients with N279K mutant frontotemporal dementia and parkinsonism linked to chromosome 17/MAPT underwent [
RESULTS
Haplotype assays revealed that these kindreds originated from a single founder. Despite homogeneity of the disease-causing MAPT allele, clinical progression was more rapid in 2 kindreds than in the other. The kindred with slow progression showed mild tau depositions, mostly confined to the midbrain and medial temporal areas. In contrast, kindreds with rapid progression showed profoundly increased [
CONCLUSIONS
[
Identifiants
pubmed: 30773680
doi: 10.1002/mds.27623
pmc: PMC6593784
doi:
Substances chimiques
MAPT protein, human
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
568-574Subventions
Organisme : Japan Agency for Medical Research and Development
ID : 15ek0109029s0202
Pays : International
Organisme : Japan Agency for Medical Research and Development
ID : 16768966
Pays : International
Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 16K09678
Pays : International
Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 26713031
Pays : International
Informations de copyright
© 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Références
Acta Neuropathol. 1999 Jul;98(1):62-77
pubmed: 10412802
Neurology. 1999 Sep 11;53(4):864-8
pubmed: 10489057
Neurology. 2000 May 9;54(9):1787-95
pubmed: 10802785
Brain. 2002 May;125(Pt 5):969-75
pubmed: 11960887
Neurology. 2002 Apr 23;58(8):1161-8
pubmed: 11971081
Arch Neurol. 2002 Jun;59(6):943-50
pubmed: 12056930
Am J Pathol. 2002 Jun;160(6):2045-53
pubmed: 12057909
Neurology. 2002 Dec 10;59(11):1791-3
pubmed: 12473774
Ann Neurol. 1992 Sep;32(3):312-20
pubmed: 1416801
Arch Neurol. 2003 Oct;60(10):1454-6
pubmed: 14568818
Neuropathology. 2004 Mar;24(1):79-86
pubmed: 15068177
Arch Neurol. 2004 Aug;61(8):1327; author reply 1327
pubmed: 15313857
Brain. 2005 Apr;128(Pt 4):752-72
pubmed: 15615814
Brain. 2007 Jun;130(Pt 6):1566-76
pubmed: 17525140
Acta Neuropathol. 1991;82(4):239-59
pubmed: 1759558
Am J Psychiatry. 2007 Oct;164(10):1577-84
pubmed: 17898350
Arch Neurol. 2007 Oct;64(10):1535-9
pubmed: 17923640
Parkinsonism Relat Disord. 2010 Jul;16(6):404-8
pubmed: 20452812
Parkinsonism Relat Disord. 2013 Jan;19(1):15-20
pubmed: 22818528
Alzheimers Res Ther. 2013 Jan 09;5(1):1
pubmed: 23302773
Lancet Neurol. 2013 Jun;12(6):609-22
pubmed: 23684085
Neuron. 2013 Sep 18;79(6):1094-108
pubmed: 24050400
Alzheimers Res Ther. 2014 Jan 02;6(1):1
pubmed: 24382028
Ann Neurol. 2015 Nov;78(5):787-800
pubmed: 26344059
Neuropathol Appl Neurobiol. 2017 Apr;43(3):200-214
pubmed: 27859539
Ann Neurol. 2017 Jan;81(1):117-128
pubmed: 27997036
Brain. 2017 Mar 1;140(3):764-780
pubmed: 28087578
Alzheimers Dement (Amst). 2016 Dec 22;6:11-20
pubmed: 28138509
Alzheimers Res Ther. 2017 Mar 31;9(1):25
pubmed: 28359327
Mov Disord. 2017 Jul;32(7):1016-1024
pubmed: 28568506
BMC Neurol. 2017 Sep 18;17(1):186
pubmed: 28923025
Ann Neurol. 2017 Oct;82(4):622-634
pubmed: 28980714
Mov Disord. 2018 Feb;33(2):273-281
pubmed: 29278274
J Nucl Med. 2018 Jun;59(6):960-966
pubmed: 29419480
Ann Neurol. 1997 Feb;41(2):277-81
pubmed: 9029080