• Neurobiology of aging · Nov 2019

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

    • Qin Chen, Bradley F Boeve, Christopher G Schwarz, Robert Reid, Nirubol Tosakulwong, Timothy G Lesnick, Jessica Bove, Patrick Brannelly, Danielle Brushaber, Giovanni Coppola, Christina Dheel, Bradford C Dickerson, Susan Dickinson, Kelley Faber, Julie Fields, Jamie Fong, Tatiana Foroud, Leah Forsberg, Ralitza H Gavrilova, Debra Gearhart, Nupur Ghoshal, Jill Goldman, Jonathan Graff-Radford, Neill R Graff-Radford, Murray Grossman, Dana Haley, Hilary W Heuer, HsiungGing-Yuek RGRDivision of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Edward Huey, David J Irwin, Clifford R Jack, David T Jones, Lynne Jones, Anna M Karydas, David S Knopman, John Kornak, Joel Kramer, Walter Kremers, Walter A Kukull, Maria Lapid, Diane Lucente, Codrin Lungu, MackenzieIan R AIRADepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Masood Manoochehri, Scott McGinnis, Bruce L Miller, Rodney Pearlman, Leonard Petrucelli, Madeline Potter, Rosa Rademakers, Eliana M Ramos, Katherine P Rankin, Katya Rascovsky, Pheth Sengdy, Leslie Shaw, Jeremy Syrjanen, Nadine Tatton, Joanne Taylor, Arthur W Toga, John Trojanowski, Sandra Weintraub, Bonnie Wong, Adam L Boxer, Howie Rosen, Zbigniew Wszolek, Kejal Kantarci, and LEFFTDS Consortium.
    • Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Department of Radiology, Mayo Clinic, Rochester, MN, USA.
    • Neurobiol. Aging. 2019 Nov 1; 83: 54-62.

    AbstractOur 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.Copyright © 2019 Elsevier Inc. All rights reserved.

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