Trajectory of lobar atrophy in asymptomatic and symptomatic GRN mutation carriers: a longitudinal MRI study.
Asymptomatic
Frontotemporal dementia
GRN
Longitudinal
Magnetic resonance image
Journal
Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
27
06
2019
revised:
03
12
2019
accepted:
06
12
2019
pubmed:
11
1
2020
medline:
24
9
2020
entrez:
11
1
2020
Statut:
ppublish
Résumé
Loss-of-function mutations in the progranulin gene (GRN) are one of the major causes of familial frontotemporal lobar degeneration. Our objective was to determine the rates and trajectories of lobar cortical atrophy from longitudinal structural magnetic resonance imaging in both asymptomatic and symptomatic GRN mutation carriers. Individuals in this study were from the ADRC and LEFFTDS studies at the Mayo Clinic. We identified 13 GRN mutation carriers (8 asymptomatic, 5 symptomatic) and noncarriers (n = 10) who had at least 2 serial T1-weighted structural magnetic resonance images and were followed annually with a median of 3 years (range 1.0-9.8 years). Longitudinal changes in lobar cortical volume were analyzed using the tensor-based morphometry with symmetric normalization (TBM-SyN) algorithm. Linear mixed-effect models were used to model cortical volume change over time among 3 groups. The annual rates of frontal (p < 0.05) and parietal (p < 0.01) lobe cortical atrophy were higher in asymptomatic GRN mutation carriers than noncarriers. The symptomatic GRN mutation carriers also had increased rates of atrophy in the frontal (p < 0.01) and parietal lobe (p < 0.01) cortices than noncarriers. In addition, greater rates of cortical atrophy were observed in the temporal lobe cortices of symptomatic GRN mutation carriers than noncarriers (p < 0.001). We found that a decline in frontal and parietal lobar cortical volume occurs in asymptomatic GRN mutation carriers and continues in the symptomatic GRN mutation carriers, whereas an increased rate of temporal lobe cortical atrophy is observed only in symptomatic GRN mutation carriers. This sequential pattern of cortical involvement in GRN mutation carriers has important implications for using imaging biomarkers of neurodegeneration as an outcome measure in potential treatment trials involving GRN mutation carriers.
Identifiants
pubmed: 31918955
pii: S0197-4580(19)30432-4
doi: 10.1016/j.neurobiolaging.2019.12.004
pmc: PMC7767622
mid: NIHMS1548376
pii:
doi:
Substances chimiques
GRN protein, human
0
Progranulins
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
42-50Subventions
Organisme : NIA NIH HHS
ID : K24 AG045333
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG040042
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG045390
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS092089
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG063911
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
Références
Brain. 2012 Mar;135(Pt 3):794-806
pubmed: 22366795
Lancet Neurol. 2008 Oct;7(10):965-74
pubmed: 18771956
J Neurochem. 2016 Aug;138 Suppl 1:32-53
pubmed: 27009575
Eur J Neurol. 2015 May;22(5):745-52
pubmed: 25683866
Neurobiol Aging. 2018 Feb;62:191-196
pubmed: 29172163
Neuroimage. 2008 Aug 15;42(2):559-67
pubmed: 18572417
Neurology. 2011 Jul 26;77(4):393-8
pubmed: 21753165
Brain. 2008 Mar;131(Pt 3):706-20
pubmed: 18234697
PLoS One. 2014 Sep 04;9(9):e106500
pubmed: 25188321
Med Image Anal. 2008 Feb;12(1):26-41
pubmed: 17659998
Neuroimage. 2005 Jul 1;26(3):839-51
pubmed: 15955494
Alzheimers Res Ther. 2018 May 24;10(1):46
pubmed: 29793546
Curr Opin Neurol. 2011 Dec;24(6):542-9
pubmed: 21986680
Brain. 2008 Nov;131(Pt 11):2957-68
pubmed: 18829698
Neuroimage. 2010 Nov 15;53(3):1070-6
pubmed: 20045477
Neuroimage Clin. 2018 May 15;19:497-506
pubmed: 29984158
JAMA Neurol. 2014 Feb;71(2):216-21
pubmed: 24343233
Neurobiol Aging. 2009 May;30(5):739-51
pubmed: 17949857
J Alzheimers Dis. 2016;51(1):249-62
pubmed: 26836150
Alzheimers Dement. 2014 Oct;10(5 Suppl):S354-S363.e1
pubmed: 24418059
Neurobiol Aging. 2019 Apr;76:115-124
pubmed: 30711674
Neurology. 2009 Mar 3;72(9):813-20
pubmed: 19255408
Neuroimage. 2002 Jan;15(1):273-89
pubmed: 11771995
J Alzheimers Dis. 2015;47(3):751-9
pubmed: 26401709
Hum Mol Genet. 2006 Oct 15;15(20):2988-3001
pubmed: 16950801
Rejuvenation Res. 2008 Jun;11(3):585-95
pubmed: 18593276
Nat Clin Pract Neurol. 2008 Aug;4(8):455-60
pubmed: 18648346
Brain Res. 2012 Oct 2;1476:172-82
pubmed: 22348647
Neurology. 2014 Jul 8;83(2):e19-26
pubmed: 25002573
Neuroimage Clin. 2016 Aug 03;12:460-5
pubmed: 27625986
Nature. 2006 Aug 24;442(7105):916-9
pubmed: 16862116
Neurobiol Aging. 2012 Oct;33(10):2506-20
pubmed: 22130207
Brain. 2017 Jun 1;140(6):1784-1791
pubmed: 28460069
Lancet Neurol. 2015 Mar;14(3):253-62
pubmed: 25662776
Neuroimage Clin. 2018 Feb 17;18:591-598
pubmed: 29845007
Nature. 2006 Aug 24;442(7105):920-4
pubmed: 16862115
Brain. 2019 Jan 1;142(1):193-208
pubmed: 30508042
Neuroimage. 2015 Dec;123:149-64
pubmed: 26275383