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; 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; A. Goate; J. Goldman; B. Gordon; N. Graff-Radford; J. Gray; J. Gurney; J. Hassenstab; M. Hirohara; D. Holtzman; R. Hornbeck; S. Houeland DiBari; T. Ikeuchi; S. Ikonomovic; G. Jerome; C. Karch; K. Kasuga; T. Kawarabayashi; W. Klunk; R. Koeppe; J-H Lee; D. Marcus; 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; 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

doi:10.1038/s41591-018-0304-3

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Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease

Journal article

Peer reviewed

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, …

Nature Medicine, Vol.25(2), pp.277-283

2019

DOI: https://doi.org/10.1038/s41591-018-0304-3

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Abstract

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.

Details

Title: Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease
Authors/Creators: O. Preische (Author/Creator) - German Center for Neurodegenerative Diseases
S.A. Schultz (Author/Creator) - Washington University in St. Louis
A. Apel (Author/Creator) - German Center for Neurodegenerative Diseases
J. Kuhle (Author/Creator) - University Hospital of Basel
S.A. Kaeser (Author/Creator) - German Center for Neurodegenerative Diseases
C. Barro (Author/Creator) - University Hospital of Basel
S. Gräber (Author/Creator) - German Center for Neurodegenerative Diseases
E. Kuder-Buletta (Author/Creator) - German Center for Neurodegenerative Diseases
C. LaFougere (Author/Creator) - German Center for Neurodegenerative Diseases
C. Laske (Author/Creator) - German Center for Neurodegenerative Diseases
J. Vöglein (Author/Creator) - Ludwig-Maximilians-Universität München
J. Levin (Author/Creator) - German Center for Neurodegenerative Diseases
C.L. Masters (Author/Creator) - Florey Institute of Neuroscience and Mental Health
R. Martins (Author/Creator) - Edith Cowan University
P.R. Schofield (Author/Creator) - Neuroscience Research Australia
M.N. Rossor (Author/Creator) - UCL Institute of Neurology
N.R. Graff-Radford (Author/Creator) - Jacksonville College
S. Salloway (Author/Creator) - Brown University
B. Ghetti (Author/Creator) - Indiana University
J.M. Ringman (Author/Creator) - Department of Neurology, Keck School of Medicine at USC, Los Angeles, CA, USA
J.M. Noble (Author/Creator) - Columbia University Irving Medical Center
J. Chhatwal (Author/Creator) - Massachusetts General Hospital
A.M. Goate (Author/Creator) - Icahn School of Medicine at Mount Sinai
T.L.S. Benzinger (Author/Creator) - Washington University in St. Louis
J.C. Morris (Author/Creator) - Washington University in St. Louis
R.J. Bateman (Author/Creator) - Washington University in St. Louis
G. Wang (Author/Creator) - Washington University in St. Louis
A.M. Fagan (Author/Creator) - Washington University in St. Louis
E.M. McDade (Author/Creator) - Washington University in St. Louis
B.A. Gordon (Author/Creator) - Washington University in St. Louis
M. Jucker (Author/Creator) - German Center for Neurodegenerative Diseases
R. Allegri (Author/Creator)
F. Amtashar (Author/Creator)
R. Bateman (Author/Creator) - Washington University in St. Louis
T. Benzinger (Author/Creator)
S. Berman (Author/Creator)
C. Bodge (Author/Creator)
S. Brandon (Author/Creator)
W. Brooks (Author/Creator)
J. Buck (Author/Creator)
V. Buckles (Author/Creator)
S. Chea (Author/Creator)
J. Chhatwal (Author/Creator) - Massachusetts General Hospital
P. Chrem (Author/Creator)
H. Chui (Author/Creator)
J. Cinco (Author/Creator)
J. Clifford (Author/Creator)
C. Cruchaga (Author/Creator)
M. D’Mello (Author/Creator)
T. Donahue (Author/Creator)
J. Douglas (Author/Creator)
N. Edigo (Author/Creator)
N. Erekin-Taner (Author/Creator)
A. Fagan (Author/Creator) - Washington University in St. Louis
M. Farlow (Author/Creator)
A. Farrar (Author/Creator)
H. Feldman (Author/Creator)
G. Flynn (Author/Creator)
N. Fox (Author/Creator)
E. Franklin (Author/Creator)
H. Fujii (Author/Creator)
C. Gant (Author/Creator)
S. Gardener (Author/Creator)
B. Ghetti (Author/Creator) - Indiana University
A. Goate (Author/Creator) - Icahn School of Medicine at Mount Sinai
J. Goldman (Author/Creator)
B. Gordon (Author/Creator) - Washington University in St. Louis
N. Graff-Radford (Author/Creator) - Jacksonville College
J. Gray (Author/Creator)
J. Gurney (Author/Creator)
J. Hassenstab (Author/Creator)
M. Hirohara (Author/Creator)
D. Holtzman (Author/Creator)
R. Hornbeck (Author/Creator)
S. Houeland DiBari (Author/Creator)
T. Ikeuchi (Author/Creator)
S. Ikonomovic (Author/Creator)
G. Jerome (Author/Creator)
M. Jucker (Author/Creator) - German Center for Neurodegenerative Diseases
C. Karch (Author/Creator)
K. Kasuga (Author/Creator)
T. Kawarabayashi (Author/Creator)
W. Klunk (Author/Creator)
R. Koeppe (Author/Creator)
E. Kuder-Buletta (Author/Creator) - German Center for Neurodegenerative Diseases
C. Laske (Author/Creator) - German Center for Neurodegenerative Diseases
J-H Lee (Author/Creator)
J. Levin (Author/Creator) - German Center for Neurodegenerative Diseases
D. Marcus (Author/Creator)
R. Martins (Author/Creator) - Edith Cowan University
N.S. Mason (Author/Creator)
C. Masters (Author/Creator) - Florey Institute of Neuroscience and Mental Health
D. Maue-Dreyfus (Author/Creator)
E. McDade (Author/Creator) - Washington University in St. Louis
L. Montoya (Author/Creator)
H. Mori (Author/Creator)
J. Morris (Author/Creator) - Washington University in St. Louis
A. Nagamatsu (Author/Creator)
K. Neimeyer (Author/Creator)
J. Noble (Author/Creator) - Columbia University Irving Medical Center
J. Norton (Author/Creator)
R. Perrin (Author/Creator)
M. Raichle (Author/Creator)
J. Ringman (Author/Creator) - Department of Neurology, Keck School of Medicine at USC, Los Angeles, CA, USA
J-H Roh (Author/Creator)
S. Salloway (Author/Creator) - Brown University
P. Schofield (Author/Creator) - Neuroscience Research Australia
H. Shimada (Author/Creator)
T. Shiroto (Author/Creator)
M. Shoji (Author/Creator)
W. Sigurdson (Author/Creator)
H. Sohrabi (Author/Creator)
P. Sparks (Author/Creator)
K. Suzuki (Author/Creator)
L. Swisher (Author/Creator)
K. Taddei (Author/Creator)
J. Wang (Author/Creator)
P. Wang (Author/Creator)
M. Weiner (Author/Creator)
M. Wolfsberger (Author/Creator)
C. Xiong (Author/Creator)
X. Xu (Author/Creator)
Publication Details: Nature Medicine, Vol.25(2), pp.277-283
Publisher: Nature Research
Identifiers: 991005543028507891
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.60 Dementia
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental
ESI research areas: Molecular Biology & Genetics