Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease
O. Preische, S.A. Schultz, A. Apel, J. Kuhle, S.A. Kaeser, C. Barro, S. Gräber, E. Kuder-Buletta, C. LaFougere, C. Laske, J. Vöglein, J. Levin, C.L. Masters , R. Martins , P.R. Schofield, M.N. Rossor, N.R. Graff-Radford, S. Salloway, B. Ghetti, J.M. Ringman, J.M. Noble, J. Chhatwal, A.M. Goate, T.L.S. Benzinger, J.C. Morris, R.J. Bateman, G. Wang, A.M. Fagan, E.M. McDade, B.A. Gordon, M. Jucker, R. Allegri, F. Amtashar, R. Bateman, T. Benzinger, S. Berman, C. Bodge, S. Brandon, W. Brooks, J. Buck, V. Buckles, S. Chea, J. Chhatwal, P. Chrem, H. Chui, J. Cinco, J. Clifford, C. Cruchaga , M. D’Mello, T. Donahue, J. Douglas, N. Edigo, N. Erekin-Taner, A. Fagan, M. Farlow, A. Farrar, H. Feldman, G. Flynn, N. Fox, E. Franklin, H. Fujii, C. Gant, S. Gardener, B. Ghetti, A. Goate, J. Goldman, B. Gordon , N. Graff-Radford, J. Gray, J. Gurney, J. Hassenstab, M. Hirohara, D. Holtzman, R. Hornbeck, S.H. DiBari, T. Ikeuchi, S. Ikonomovic, G. Jerome, M. Jucker, C. Karch, K. Kasuga , T. Kawarabayashi, W. Klunk, R. Koeppe, E. Kuder-Buletta, C. Laske, J.-H. Lee, J. Levin, D. Marcus, R. Martins, N.S. Mason, C. Masters, D. Maue-Dreyfus, E. McDade, L. Montoya, H. Mori, J. Morris , A. Nagamatsu, K. Neimeyer, J. Noble, J. Norton, R. Perrin, M. Raichle, J. Ringman, J.H. Roh, S. Salloway, P. Schofield, H. Shimada, T. Shiroto, M. Shoji, W. Sigurdson, H. Sohrabi, P. Sparks, K. Suzuki, L. Swisher, K. Taddei, J. Wang, P. Wang, M. Weiner, M. Wolfsberger, C. Xiong, X. Xu, N
This research validates the initial observations that Neurofilament light chain (NfL) is a promising fluid biomarker for disease progression for various cerebral proteopathies. Using the DIAN cohort and an ultrasensitive immunoassay this demonstrates that NfL in cerebrospinal fluid (CSF) and serum are elevated in the presymptomatic stages of familial Alzheimer's disease. The rate of change in serum NfL is more informative than cross-sectional absolute NfL levels, detecting changes in a timeline of 16.2 years versus 6.8 years before symptom onset. The increased rate of change in NfL was strongly associated with cortical thinning measurements determined by MRI, but less with amyloid-β-deposition or glucose metabolism via PET. Overall, this important paper demonstrates that NfL dynamics in serum predict disease progression and neurodegeneration at the early presymptomatic stages of familial Alzheimer'd disease, and is a potentially useful biomarker.