The Study
Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer’s disease
This study watched people with a rare inherited form of Alzheimer’s for many years and saw that a protein in their blood and spinal fluid changed as their brain got worse. It doesn’t prove the protein causes the damage — it just shows they happen together.
Analysis score
Maximum 72 for a cohort study.
Where the score came from
Scientists tracked a protein in blood and spinal fluid that leaks out when brain cells die. They found it rises years before people feel symptoms of Alzheimer’s.
Where does this study sit?
Reviews of RCTs (Meta-analyses)
Max 100Randomized Trials
Max 90Reviews of Cohort Studies
Max 85Cohort Studies
Max 72Reviews of Case-Control Studies
Max 63Case-Control Studies
Max 58Cross-Sectional & Case Series
Max 50Expert Opinion
Max 566 / 100
Quality score
Groups of people are followed over time to see who develops an outcome. Strong for identifying risk factors and associations, but cannot prove causation as firmly as RCTs.
Key takeaways
Summary
Based on the study abstract and findings.
- 1This means a simple blood test can warn of Alzheimer’s very early, but once symptoms appear, spinal fluid gives a more accurate picture of how fast the brain is deteriorating.
- 2The protein rises 18.9 years before symptoms in blood, and 24.6 years before in spinal fluid.
- 3After symptoms start, spinal fluid levels keep rising, but blood levels stop going up.
Score breakdown, methodology, conflicts of interest, evidence analysis & raw study data
Publication
Journal
Nature Communications
Year
2024
Authors
Anna Hofmann, Lisa M. Häsler, Marius Lambert, S. Kaeser, Susanne Gräber‐Sultan, Ulrike Obermüller, Elke Kuder-Buletta, C. la Fougère, C. Laske, Jonathan Vöglein, J. Levin, Nick C. Fox, Natalie S. Ryan, H. Zetterberg, J. Llibre-Guerra, Richard J. Perrin, L. Ibanez, Peter R. Schofield, W. Brooks, Gregg S. Day, Martin R. Farlow, R. Allegri, P. Chrem Mendez, Takeshi Ikeuchi, K. Kasuga, Jae-Hong Lee, J. Roh, Hiroshi Mori, Francisco Lopera, Randall J. Bateman, E. McDade, B. Gordon, J. Chhatwal, Mathias Jucker, Stephanie A. Schultz, David Andrew J. Bryce Nicolas Randall Jacob A. Tammie Sa Aguillon Aschenbrenner Baker Barthelemy Bateman Be, D. Aguillón, A. Aschenbrenner, Bryce Baker, N. Barthélemy, Randall J. Bateman, Jacob Bechara, T. Benzinger, S. Berman, David M. Cash, Allison Chen, Charles D. Chen, Jasmeer P. Chhatwal Chhatwal, Patricio Chrem Mendez, L. Courtney, C. Cruchaga, Alisha J. Daniels, Gregg S. Day, Anne M. Fagan, Martin R. Farlow, Shaney Flores, E. Franklin, A. Goate, Susanne Graber-Sultan, N. Graff-Radford, Emily Gremminger, Jason J Hassenstab, Elizabeth M. Herries, David M. Holtzman, Russ C. Hornbeck, E. Huey, S. Ikonomovic, Kelley Jackson, Steve Jarman, Gina Jerome, E. Johnson, N. Joseph-Mathurin, Celeste M. Karch, S. Keefe, Deborah Koudelis, Y. Leon, A. Levey, Yan Li, Ruijin Lu, Jacob A. Marsh, Ralph N. Martins, Parinaz Massoumzadeh, C. Masters, Austin McCullough, Nicole S Mckay, Matthew Minton, John C. Morris, N. Nadkarni, J. Nicklaus, Yoshiki Niimi, James M Noble, Ulrike Obermueller, Danielle M. Picarello, Christine Pulizos, Laura Ramirez, A. Renton, J. Ringman, Jacqueline Rizzo, Yvonne Roedenbeck, P. Rosa-Neto, Edita Sabaredzovic, S. Salloway, R. Sánchez-Valle, Jalen Scott, Nicholas T. Seyfried, A. Simmons, Jennifer Smith, H. Smith, Jennifer Stauber, Sarah Stout, C. Supnet‐Bell, E. Surace, Silvia Vazquez, Jonathan Vöglein, Guoqiao Wang, Qing Wang, Chengie Xiong, Xiong Xu, Jinbin Xu
Related Content
Claims (6)
Blood levels of neurofilament light chain rise 9 to 10 years before a person is diagnosed with Alzheimer's disease, indicating that nerve cell damage is already occurring.
In people with inherited Alzheimer’s disease, levels of neurofilament light chain in cerebrospinal fluid and blood increase together 10 to 20 years before symptoms appear and both correlate with loss of brain gray matter. After symptoms begin, blood levels stabilize but cerebrospinal fluid levels keep rising, showing that cerebrospinal fluid neurofilament light chain more accurately reflects ongoing nerve cell damage during the symptomatic phase.
In people with inherited Alzheimer’s disease, levels of neurofilament light chain in spinal fluid and blood are closely linked before symptoms appear, but this link becomes much weaker after symptoms start, meaning blood levels are less accurate for tracking brain degeneration once the disease is active.
In people with inherited Alzheimer’s disease, higher levels of neurofilament light chain in spinal fluid and blood correlate with faster loss of brain tissue during symptom onset, but not with the amount of amyloid-beta protein buildup.
In people with inherited Alzheimer’s disease, levels of neurofilament light chain in cerebrospinal fluid rise about 24.6 years before symptoms appear, while levels in plasma rise about 18.9 years before symptoms, showing that cerebrospinal fluid levels increase earlier than plasma levels.
In people with inherited Alzheimer’s disease, the ratio of neurofilament light chain in blood versus spinal fluid drops significantly when symptoms appear, reflecting a change in how this protein moves from the brain into the bloodstream.
Not medical advice. For informational purposes only. Always consult a qualified healthcare professional before making health decisions.