TY - JOUR
T1 - Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease
AU - Preische, Oliver
AU - Schultz, Stephanie A.
AU - Apel, Anja
AU - Kuhle, Jens
AU - Kaeser, Stephan A.
AU - Barro, Christian
AU - Gräber, Susanne
AU - Kuder-Buletta, Elke
AU - LaFougere, Christian
AU - Laske, Christoph
AU - Vöglein, Jonathan
AU - Levin, Johannes
AU - Masters, Colin L.
AU - Martins, Ralph
AU - Schofield, Peter R.
AU - Rossor, Martin N.
AU - Graff-Radford, Neill R.
AU - Salloway, Stephen
AU - Ghetti, Bernardino
AU - Ringman, John M.
AU - Noble, James M.
AU - Chhatwal, Jasmeer
AU - Goate, Alison M.
AU - Benzinger, Tammie L.S.
AU - Morris, John C.
AU - Bateman, Randall J.
AU - Wang, Guoqiao
AU - Fagan, Anne M.
AU - McDade, Eric M.
AU - Gordon, Brian A.
AU - Jucker, Mathias
AU - Dominantly Inherited Alzheimer Network
AU - Allegri, Ricardo
AU - Amtashar, Fatima
AU - Berman, Sarah
AU - Bodge, Courtney
AU - Brandon, Susan
AU - Brooks, William
AU - Buck, Jill
AU - Buckles, Virginia
AU - Chea, Sochenda
AU - Chrem, Patricio
AU - Chui, Helena
AU - Cinco, Jake
AU - Clifford, Jack
AU - Cruchaga, Carlos
AU - D’Mello, Mirelle
AU - Donahue, Tamara
AU - Douglas, Jane
AU - Edigo, Noelia
AU - Erekin-Taner, Nilufer
AU - Farlow, Marty
AU - Farrar, Angela
AU - Feldman, Howard
AU - Flynn, Gigi
AU - Fox, Nick
AU - Franklin, Erin
AU - Fujii, Hisako
AU - Gant, Cortaiga
AU - Gardener, Samantha
AU - Goldman, Jill
AU - Gray, Julia
AU - Gurney, Jenny
AU - Hassenstab, Jason
AU - Hirohara, Mie
AU - Holtzman, David
AU - Hornbeck, Russ
AU - DiBari, Siri Houeland
AU - Ikeuchi, Takeshi
AU - Ikonomovic, Snezana
AU - Jerome, Gina
AU - Karch, Celeste
AU - Kasuga, Kensaku
AU - Kawarabayashi, Takeshi
AU - Klunk, William
AU - Koeppe, Robert
AU - Lee, Jae-Hong
AU - Marcus, Daniel
AU - Mason, Neal Scott
AU - Maue-Dreyfus, Denise
AU - Montoya, Lucy
AU - Mori, Hiroshi
AU - Nagamatsu, Akem
AU - Neimeyer, Katie
AU - Norton, Joanne
AU - Perrin, Richard
AU - Raichle, Marc
AU - Roh, Jee Hoon
AU - Shimada, Hiroyuki
AU - Shiroto, Tomoyo
AU - Shoji, Mikio
AU - Sigurdson, Wendy
AU - Sohrabi, Hamid
AU - Sparks, Paige
AU - Suzuki, Kazushi
AU - Swisher, Laura
AU - Taddei, Kevin
AU - Wang, Jen
AU - Wang, Peter
AU - Weiner, Mike
AU - Wolfsberger, Mary
AU - Xiong, Chengjie
AU - Xu, Xiong
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer’s disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini–Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer’s disease, which supports its potential utility as a clinically useful biomarker.
AB - Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer’s disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini–Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer’s disease, which supports its potential utility as a clinically useful biomarker.
UR - http://www.scopus.com/inward/record.url?scp=85060347238&partnerID=8YFLogxK
U2 - 10.1038/s41591-018-0304-3
DO - 10.1038/s41591-018-0304-3
M3 - Article
C2 - 30664784
AN - SCOPUS:85060347238
SN - 1078-8956
VL - 25
SP - 277
EP - 283
JO - Nature Medicine
JF - Nature Medicine
IS - 2
ER -