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

Oliver Preische, Stephanie A. Schultz, Anja Apel, Jens Kuhle, Stephan A. Kaeser, Christian Barro, Susanne Gräber, Elke Kuder-Buletta, Christian LaFougere, Christoph Laske, Jonathan Vöglein, Johannes Levin, Colin L. Masters, Ralph Martins, Peter R. Schofield, Martin N. Rossor, Neill R. Graff-Radford, Stephen Salloway, Bernardino Ghetti, John M. Ringman, James M. Noble, Jasmeer Chhatwal, Alison M. Goate, Tammie L. S. Benzinger, John C. Morris, Randall J. Bateman, Guoqiao Wang, Anne M. Fagan, Eric M. McDade, Brian A. Gordon, Mathias Jucker & Dominantly Inherited Alzheimer Network. Nature Medicine 2019 Read More

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. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

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Posted on January 31, 2019
Posted in: HPAN, Neurodegeneration, Publications Authors: , , , , , , , ,