TY - JOUR
T1 - Tracking white matter degeneration in asymptomatic and symptomatic MAPT mutation carriers
AU - LEFFTDS Consortium
AU - Chen, Qin
AU - Boeve, Bradley F.
AU - Schwarz, Christopher G.
AU - Reid, Robert
AU - Tosakulwong, Nirubol
AU - Lesnick, Timothy G.
AU - Bove, Jessica
AU - Brannelly, Patrick
AU - Brushaber, Danielle
AU - Coppola, Giovanni
AU - Dheel, Christina
AU - Dickerson, Bradford C.
AU - Dickinson, Susan
AU - Faber, Kelley
AU - Fields, Julie
AU - Fong, Jamie
AU - Foroud, Tatiana
AU - Forsberg, Leah
AU - Gavrilova, Ralitza H.
AU - Gearhart, Debra
AU - Ghoshal, Nupur
AU - Goldman, Jill
AU - Graff-Radford, Jonathan
AU - Graff-Radford, Neill R.
AU - Grossman, Murray
AU - Haley, Dana
AU - Heuer, Hilary W.
AU - Hsiung, Ging Yuek R.
AU - Huey, Edward
AU - Irwin, David J.
AU - Jack, Clifford R.
AU - Jones, David T.
AU - Jones, Lynne
AU - Karydas, Anna M.
AU - Knopman, David S.
AU - Kornak, John
AU - Kramer, Joel
AU - Kremers, Walter
AU - Kukull, Walter A.
AU - Lapid, Maria
AU - Lucente, Diane
AU - Lungu, Codrin
AU - Mackenzie, Ian R.A.
AU - Manoochehri, Masood
AU - McGinnis, Scott
AU - Miller, Bruce L.
AU - Petrucelli, Leonard
AU - Rademakers, Rosa V
AU - Wszolek, Zbigniew
AU - Kantarci, Kejal
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/11
Y1 - 2019/11
N2 - 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.
AB - 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.
KW - Asymptomatic
KW - Diffusion tensor image
KW - Frontotemporal dementia
KW - Longitudinal
KW - MAPT
UR - http://www.scopus.com/inward/record.url?scp=85072730982&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072730982&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2019.08.011
DO - 10.1016/j.neurobiolaging.2019.08.011
M3 - Article
C2 - 31585367
AN - SCOPUS:85072730982
SN - 0197-4580
VL - 83
SP - 54
EP - 62
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -