Journal article
Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease
Nature Medicine, Vol.25(2), pp.277-283
2019
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 DiseasesS.A. Schultz (Author/Creator) - Washington University in St. LouisA. Apel (Author/Creator) - German Center for Neurodegenerative DiseasesJ. Kuhle (Author/Creator) - University Hospital of BaselS.A. Kaeser (Author/Creator) - German Center for Neurodegenerative DiseasesC. Barro (Author/Creator) - University Hospital of BaselS. Gräber (Author/Creator) - German Center for Neurodegenerative DiseasesE. Kuder-Buletta (Author/Creator) - German Center for Neurodegenerative DiseasesC. LaFougere (Author/Creator) - German Center for Neurodegenerative DiseasesC. Laske (Author/Creator) - German Center for Neurodegenerative DiseasesJ. Vöglein (Author/Creator) - Ludwig-Maximilians-Universität MünchenJ. Levin (Author/Creator) - German Center for Neurodegenerative DiseasesC.L. Masters (Author/Creator) - Florey Institute of Neuroscience and Mental HealthR. Martins (Author/Creator) - Edith Cowan UniversityP.R. Schofield (Author/Creator) - Neuroscience Research AustraliaM.N. Rossor (Author/Creator) - UCL Institute of NeurologyN.R. Graff-Radford (Author/Creator) - Jacksonville CollegeS. Salloway (Author/Creator) - Brown UniversityB. Ghetti (Author/Creator) - Indiana UniversityJ.M. Ringman (Author/Creator) - Department of Neurology, Keck School of Medicine at USC, Los Angeles, CA, USAJ.M. Noble (Author/Creator) - Columbia University Irving Medical CenterJ. Chhatwal (Author/Creator) - Massachusetts General HospitalA.M. Goate (Author/Creator) - Icahn School of Medicine at Mount SinaiT.L.S. Benzinger (Author/Creator) - Washington University in St. LouisJ.C. Morris (Author/Creator) - Washington University in St. LouisR.J. Bateman (Author/Creator) - Washington University in St. LouisG. Wang (Author/Creator) - Washington University in St. LouisA.M. Fagan (Author/Creator) - Washington University in St. LouisE.M. McDade (Author/Creator) - Washington University in St. LouisB.A. Gordon (Author/Creator) - Washington University in St. LouisM. Jucker (Author/Creator) - German Center for Neurodegenerative DiseasesR. Allegri (Author/Creator)F. Amtashar (Author/Creator)R. Bateman (Author/Creator) - Washington University in St. LouisT. 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 HospitalP. 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. LouisM. 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 UniversityA. Goate (Author/Creator) - Icahn School of Medicine at Mount SinaiJ. Goldman (Author/Creator)B. Gordon (Author/Creator) - Washington University in St. LouisN. Graff-Radford (Author/Creator) - Jacksonville CollegeJ. 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 DiseasesC. 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 DiseasesC. Laske (Author/Creator) - German Center for Neurodegenerative DiseasesJ-H Lee (Author/Creator)J. Levin (Author/Creator) - German Center for Neurodegenerative DiseasesD. Marcus (Author/Creator)R. Martins (Author/Creator) - Edith Cowan UniversityN.S. Mason (Author/Creator)C. Masters (Author/Creator) - Florey Institute of Neuroscience and Mental HealthD. Maue-Dreyfus (Author/Creator)E. McDade (Author/Creator) - Washington University in St. LouisL. Montoya (Author/Creator)H. Mori (Author/Creator)J. Morris (Author/Creator) - Washington University in St. LouisA. Nagamatsu (Author/Creator)K. Neimeyer (Author/Creator)J. Noble (Author/Creator) - Columbia University Irving Medical CenterJ. 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, USAJ-H Roh (Author/Creator)S. Salloway (Author/Creator) - Brown UniversityP. Schofield (Author/Creator) - Neuroscience Research AustraliaH. 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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- 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