Journal Article (Letter)

DZNE-2020-06795

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease.

Preische, O. (First author)DZNE* ; Schultz, S. A. ; Apel, A.DZNE* ; Kuhle, J. ; Kaeser, S. A.DZNE* ; Barro, C. ; Gräber, S.DZNE* ; Kuder-Buletta, E.DZNE* ; la Fougère, C.DZNE* ; Laske, C.DZNE* ; Vöglein, J.DZNE* ; Levin, J.DZNE* ; Masters, C. L. ; Martins, R. ; Schofield, P. R. ; Rossor, M. N. ; Graff-Radford, N. R. ; Salloway, S. ; Ghetti, B. ; Ringman, J. M. ; Noble, J. M. ; Chhatwal, J. ; Goate, A. M. ; Benzinger, T. L. S. ; Morris, J. C. ; Bateman, R. J. ; Wang, G. ; Fagan, A. M. ; McDade, E. M. ; Gordon, B. A. ; Jucker, M. (Corresponding author)DZNE* ; Network, D. I. A. ; Allegri, R. ; Amtashar, F. ; Bateman, R. ; Benzinger, T. ; Berman, S. ; Bodge, C. ; Brandon, S. ; Brooks, W. ; Buck, J. ; Buckles, V. ; Chea, S. ; Chhatwal, J. ; Chrem, P. ; Chui, H. ; Cinco, J. ; Clifford, J. ; Cruchaga, C. ; D'Mello, M. ; Donahue, T. ; Douglas, J. ; Edigo, N. ; Erekin-Taner, N. ; Fagan, A. ; Farlow, M. ; Farrar, A. ; Feldman, H. ; Flynn, G. ; Fox, N. ; Franklin, E. ; Fujii, H. ; Gant, C. ; Gardener, S. ; Ghetti, B. ; Goate, A. ; Goldman, J. ; Gordon, B. ; Graff-Radford, N. ; Gray, J. ; Gurney, J. ; Hassenstab, J. ; Hirohara, M. ; Holtzman, D. ; Hornbeck, R. ; DiBari, S. H.DZNE* ; Ikeuchi, T. ; Ikonomovic, S. ; Jerome, G. ; Karch, C. ; Kasuga, K. ; Kawarabayashi, T. ; Klunk, W. ; Koeppe, R. ; Kuder-Buletta, E. ; Lee, J.-H. ; Marcus, D. ; Martins, R. ; Mason, N. S. ; Masters, C. ; Maue-Dreyfus, D. ; McDade, E. ; Montoya, L. ; Mori, H. ; Morris, J. ; Nagamatsu, A. ; Neimeyer, K. ; Noble, J. ; Norton, J. ; Perrin, R. ; Raichle, M. ; Ringman, J. ; Roh, J. H. ; Salloway, S. ; Schofield, P. ; Shimada, H. ; Shiroto, T. ; Shoji, M. ; Sigurdson, W. ; Sohrabi, H. ; Sparks, P. ; Suzuki, K. ; Swisher, L. ; Taddei, K. ; Wang, J. ; Wang, P. ; Weiner, M. ; Wolfsberger, M. ; Xiong, C. ; Xu, X.

2019
Nature America Inc. New York, NY

This record in other databases:    

Please use a persistent id in citations: doi:10.1038/s41591-018-0304-3

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.

Keyword(s): Alzheimer Disease: blood (MeSH) ; Alzheimer Disease: cerebrospinal fluid (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Disease Progression (MeSH) ; Humans (MeSH) ; Mutation: genetics (MeSH) ; Nerve Degeneration: blood (MeSH) ; Neurofilament Proteins: blood (MeSH) ; Neurofilament Proteins: cerebrospinal fluid (MeSH) ; Neurofilament Proteins: genetics (MeSH) ; Neurofilament Proteins ; neurofilament protein L

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Contributing Institute(s):

1. Cell Biology of Neurological Diseases (AG Jucker)
2. Core ICRU (Core ICRU)
3. Tübingen common (Tübingen common)
4. Translational Neurodegeneration (AG Höglinger 1)
5. Clinical Research (Munich) (Clinical Research (Munich))
6. Clinical Neurodegeneration (AG Levin)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)
2. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 80 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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