@article{f284e6e184194bed968ac705e21559b5,
title = "Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer{\textquoteright}s disease",
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{\textquoteright}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{\textquoteright}s disease, which supports its potential utility as a clinically useful biomarker.",
author = "{Dominantly Inherited Alzheimer Network} and Oliver Preische and Schultz, {Stephanie A.} and Anja Apel and Jens Kuhle and Kaeser, {Stephan A.} and Christian Barro and Susanne Gr{\"a}ber and Elke Kuder-Buletta and Christian LaFougere and Christoph Laske and Jonathan V{\"o}glein and Johannes Levin and Masters, {Colin L.} and Ralph Martins and Schofield, {Peter R.} and Rossor, {Martin N.} and Graff-Radford, {Neill R.} and Stephen Salloway and Bernardino Ghetti and Ringman, {John M.} and Noble, {James M.} and Jasmeer Chhatwal and Goate, {Alison M.} and Benzinger, {Tammie L.S.} and Morris, {John C.} and Bateman, {Randall J.} and Guoqiao Wang and Fagan, {Anne M.} and McDade, {Eric M.} and Gordon, {Brian A.} and Mathias Jucker and Ricardo Allegri and Fatima Amtashar and Sarah Berman and Courtney Bodge and Susan Brandon and William Brooks and Jill Buck and Virginia Buckles and Sochenda Chea and Patricio Chrem and Helena Chui and Jake Cinco and Jack Clifford and Carlos Cruchaga and Mirelle D{\textquoteright}Mello and Tamara Donahue and Jane Douglas and Noelia Edigo and Jen Wang",
note = "Funding Information: We would like to thank M. Staufenbiel and M. Eichner for support and helpful comments and C. Haass and M. Suarez (Munich) for experimental and logistic support. Data collection and sharing for this project was supported by DIAN (grant no. UF1AG032438) funded by the National Institute on Aging and the German Center for Neurodegenerative Diseases (DZNE). Additional support came from the National Institutes of Health-funded NINDS Center Core for Brain Imaging (grant no. P30NS098577), the National Science Foundation (grant no. DGE-1745038), National Institutes of Health (grant no. UL1TR001873 to J.M.N.), the Swiss National Science Foundation (grant no. 320030-160221 to J.K.), the National Institute for Health Research University College London Hospitals Biomedical Research Centre, and the MRC Dementias Platform UK (grant nos. MR/L023784/1 and MR/009076/1). We acknowledge the altruism of the participants Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2019",
month = feb,
day = "1",
doi = "10.1038/s41591-018-0304-3",
language = "English",
volume = "25",
pages = "277--283",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "2",
}