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Tracking white matter degeneration in asymptomatic and symptomatic MAPT mutation carriers.

Authors :
Chen Q
Boeve BF
Schwarz CG
Reid R
Tosakulwong N
Lesnick TG
Bove J
Brannelly P
Brushaber D
Coppola G
Dheel C
Dickerson BC
Dickinson S
Faber K
Fields J
Fong J
Foroud T
Forsberg L
Gavrilova RH
Gearhart D
Ghoshal N
Goldman J
Graff-Radford J
Graff-Radford NR
Grossman M
Haley D
Heuer HW
Hsiung GR
Huey E
Irwin DJ
Jack CR
Jones DT
Jones L
Karydas AM
Knopman DS
Kornak J
Kramer J
Kremers W
Kukull WA
Lapid M
Lucente D
Lungu C
Mackenzie IRA
Manoochehri M
McGinnis S
Miller BL
Pearlman R
Petrucelli L
Potter M
Rademakers R
Ramos EM
Rankin KP
Rascovsky K
Sengdy P
Shaw L
Syrjanen J
Tatton N
Taylor J
Toga AW
Trojanowski J
Weintraub S
Wong B
Boxer AL
Rosen H
Wszolek Z
Kantarci K
Source :
Neurobiology of aging [Neurobiol Aging] 2019 Nov; Vol. 83, pp. 54-62. Date of Electronic Publication: 2019 Aug 15.
Publication Year :
2019

Abstract

Our aim was to investigate the patterns and trajectories of white matter (WM) diffusion abnormalities in microtubule-associated protein tau (MAPT) mutations carriers. We studied 22 MAPT mutation carriers (12 asymptomatic, 10 symptomatic) and 20 noncarriers from 8 families, who underwent diffusion tensor imaging (DTI) and a subset (10 asymptomatic, 6 symptomatic MAPT mutation carriers, and 10 noncarriers) were followed annually (median = 4 years). Cross-sectional and longitudinal changes in mean diffusivity (MD) and fractional anisotropy were analyzed. Asymptomatic MAPT mutation carriers had higher MD in entorhinal WM, which propagated to the limbic tracts and frontotemporal projections in the symptomatic stage compared with noncarriers. Reduced fractional anisotropy and increased MD in the entorhinal WM were associated with the proximity to estimated and actual age of symptom onset. The annualized change of entorhinal MD on serial DTI was accelerated in MAPT mutation carriers compared with noncarriers. Entorhinal WM diffusion abnormalities precede the symptom onset and track with disease progression in MAPT mutation carriers. Our cross-sectional and longitudinal data showed a potential clinical utility for DTI to track neurodegenerative disease progression for MAPT mutation carriers in clinical trials.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1558-1497
Volume :
83
Database :
MEDLINE
Journal :
Neurobiology of aging
Publication Type :
Academic Journal
Accession number :
31585367
Full Text :
https://doi.org/10.1016/j.neurobiolaging.2019.08.011