1. Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease
- Author
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Preische, Oliver, Schultz, Stephanie A, Vöglein, Jonathan, Raichle, Marc, Ringman, John, Roh, Jee Hoon, Salloway, Stephen, Schofield, Peter, Shimada, Hiroyuki, Shiroto, Tomoyo, Shoji, Mikio, Sigurdson, Wendy, Sohrabi, Hamid, Levin, Johannes, Sparks, Paige, Suzuki, Kazushi, Swisher, Laura, Taddei, Kevin, Wang, Jen, Wang, Peter, Weiner, Mike, Wolfsberger, Mary, Xiong, Chengjie, Xu, Xiong, Masters, Colin L, Martins, Ralph, Schofield, Peter R, Rossor, Martin N, Graff-Radford, Neill R, Ghetti, Bernardino, Ringman, John M, Apel, Anja, Noble, James M, Chhatwal, Jasmeer, Goate, Alison M, Benzinger, Tammie L S, Morris, John C, Bateman, Randall J, Wang, Guoqiao, Fagan, Anne M, McDade, Eric M, Gordon, Brian A, Kuhle, Jens, Jucker, Mathias, Network, Dominantly Inherited Alzheimer, Allegri, Ricardo, Amtashar, Fatima, Bateman, Randall, Benzinger, Tammie, Berman, Sarah, Bodge, Courtney, Brandon, Susan, Brooks, William, Kaeser, Stephan A, Buck, Jill, Buckles, Virginia, Chea, Sochenda, Chrem, Patricio, Chui, Helena, Cinco, Jake, Clifford, Jack, Cruchaga, Carlos, D'Mello, Mirelle, Barro, Christian, Donahue, Tamara, Douglas, Jane, Edigo, Noelia, Erekin-Taner, Nilufer, Fagan, Anne, Farlow, Marty, Farrar, Angela, Feldman, Howard, Flynn, Gigi, Fox, Nick, Gräber, Susanne, Franklin, Erin, Fujii, Hisako, Gant, Cortaiga, Gardener, Samantha, Goate, Alison, Goldman, Jill, Gordon, Brian, Graff-Radford, Neill, Gray, Julia, Kuder-Buletta, Elke, Gurney, Jenny, Hassenstab, Jason, Hirohara, Mie, Holtzman, David, Hornbeck, Russ, DiBari, Siri Houeland, Ikeuchi, Takeshi, Ikonomovic, Snezana, Jerome, Gina, Karch, Celeste, la Fougère, Christian, Kasuga, Kensaku, Kawarabayashi, Takeshi, Klunk, William, Koeppe, Robert, Lee, Jae-Hong, Marcus, Daniel, Mason, Neal Scott, Masters, Colin, Laske, Christoph, Maue-Dreyfus, Denise, McDade, Eric, Montoya, Lucy, Mori, Hiroshi, Morris, John, Nagamatsu, Akem, Neimeyer, Katie, Noble, James, Norton, Joanne, and Perrin, Richard
- Subjects
0301 basic medicine ,Oncology ,Aging ,blood [Neurofilament Proteins] ,Neurofilament ,Medicina Clínica ,Disease ,Neurodegenerative ,Alzheimer's Disease ,Medical and Health Sciences ,pathology [Alzheimer Disease] ,0302 clinical medicine ,Cerebrospinal fluid ,Neurofilament Proteins ,2.1 Biological and endogenous factors ,Aetiology ,screening and diagnosis ,medicine.diagnostic_test ,Neurodegeneration ,General Medicine ,genetics [Neurofilament Proteins] ,cerebrospinal fluid [Alzheimer Disease] ,Detection ,Editorial Commentary ,Positron emission tomography ,030220 oncology & carcinogenesis ,Neurological ,Disease Progression ,Biomarker (medicine) ,Alzheimer's disease ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,Immunology ,blood [Nerve Degeneration] ,genetics [Mutation] ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,blood [Alzheimer Disease] ,Clinical Research ,Alzheimer Disease ,Internal medicine ,Acquired Cognitive Impairment ,medicine ,Humans ,ddc:610 ,neurofilament protein L ,business.industry ,Multiple sclerosis ,Neurosciences ,Neurología Clínica ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Magnetic resonance imaging ,medicine.disease ,Brain Disorders ,4.1 Discovery and preclinical testing of markers and technologies ,cerebrospinal fluid [Neurofilament Proteins] ,Good Health and Well Being ,030104 developmental biology ,Dominantly Inherited Alzheimer Network ,Mutation ,Nerve Degeneration ,Alzheimer ,Dementia ,business ,Biomarkers - 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. Fil: Preische, Oliver. German Center For Neurodegenerative Disease; Alemania. Eberhard Karls Universität Tübingen.; Alemania Fil: Schultz, Stephanie A.. Washington University in St. Louis; Estados Unidos Fil: Apel, Anja. German Center For Neurodegenerative Disease; Alemania. Eberhard Karls Universität Tübingen.; Alemania Fil: Kuhle, Jens. University of Basel; Suiza Fil: Kaeser, Stephan A.. German Center For Neurodegenerative Disease; Alemania. Eberhard Karls Universität Tübingen.; Alemania Fil: Barro, Christian. University of Basel; Suiza Fil: Gräber, Susanne. German Center For Neurodegenerative Disease; Alemania Fil: Kuder Buletta, Elke. German Center For Neurodegenerative Disease; Alemania Fil: LaFougere, Christian. German Center For Neurodegenerative Disease; Alemania Fil: Laske, Christoph. German Center For Neurodegenerative Disease; Alemania. Eberhard Karls Universität Tübingen.; Alemania Fil: Vöglein, Jonathan. German Center for Neurodegenerative Diseases; Alemania. Ludwig Maximilians Universitat; Alemania Fil: Levin, Johannes. German Center for Neurodegenerative Diseases; Alemania. Ludwig Maximilians Universitat; Alemania Fil: Masters, Colin. University of Melbourne; Australia Fil: Martins, Ralph. Edith Cowan University; Australia. Macquarie University; Australia Fil: Schofield, Peter. Neuroscience Research Australia; Australia. University of New South Wales; Australia Fil: Rossor, Martin N.. University College London; Estados Unidos Fil: Graff Radford, Neill. Mayo Clinic Jacksonville. Department of Neurology; Estados Unidos Fil: Salloway, Stephen. Brown University; Estados Unidos Fil: Ghetti, Bernardino. Indiana University. School of Medicine; Estados Unidos Fil: Ringman, John M.. Indiana University. School of Medicine; Estados Unidos Fil: Noble, James M.. Columbia University; Estados Unidos Fil: Chhatwal, Jasmeer. Harvard Medical School; Estados Unidos Fil: Goate, Alison. Icahn School of Medicine at Mount Sinai. Department of Neuroscience; Estados Unidos Fil: Benzinger, Tammie L. S.. Washington University in St. Louis; Estados Unidos Fil: Morris, John. Washington University in St. Louis; Estados Unidos Fil: Bateman, Randall J.. Washington University in St. Louis; Estados Unidos Fil: Wang, Guoqiao. Washington University in St. Louis; Estados Unidos Fil: Fagan, Anne M.. Washington University in St. Louis; Estados Unidos Fil: McDade, Eric M.. Washington University in St. Louis; Estados Unidos Fil: Gordon, Brian. Washington University in St. Louis; Estados Unidos Fil: Jucker, Mathias. University of Tübingen. Hertie Institute for Clinical Brain Research. Department of Cellular Neurology and Department of Psychiatry and Psychotherapy; Alemania. German Center For Neurodegenerative Disease; Alemania Fil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
- Published
- 2019