Posted on Jan 21, 2019, 8 p.m.
A protein found within blood may be used to precisely monitor disease progression of Alzheimer’s disease long before the appearance of clinical signs offering new possibilities for testing therapies, as published in the journal Nature Medicine.
Working in collaboration researchers from the Hertie Institute for Clinical Brain Research, the University Hospital Tuebingen, Washington University School of Medicine, the German Center for Neurodegenerative Diseases, and other institutions from around the globe designed the study to develop better treatments and reliable methods in which to monitor and predict the course of AD before symptoms such as memory change occur.
Blood testing is better suited for this rather than expensive brains scan, such as recent progress being shown in development of these tests most of which being based on amyloid proteins. However the team opted to take a different approach looking at neurodegeneration and the death of neurons.
When brain cells die their remains can be detected in the blood however they rapidly degrade with exception to a small piece of neurofilament that is surprisingly resistant to degradation. The team was able to show that these neurofilaments accumulate in the blood long before the onset of clinical symptoms, and that it sensitively reflects the course of disease and enables prediction of future developments based on analysis of data and samples from 405 patients.
Development of neurofilament concentration was monitored from year to year in the 405 subjects. There were noticeable changes in the blood up to 16 years before the calculated onset of dementia symptoms. This was not neurofilament concentration rather temporal evolution which is meaningful as it allows prediction of future disease progression. Further investigations showed the changes in neurofilament concentrations to reflect neural degradation accurately and allowed for predictions on how brain damaged will develop, such as brain mass loss and cognitive changes that actually occurred two years later.
The rate of change in neurofilament concentration was closely linked to brain degradation, correlation with deposition of toxic amyloid protein was less pronounced, supporting the theory of amyloid proteins triggering disease and neuronal degradation occurring independently.
This test is only suitable for diagnosing AD even though the neurofilaments accumulate in the blood in the course of other neurodegenerative disorders, and should be a powerful instrument for investigating therapies in clinical trials, according to the team.
Materials provided by DZNE - German Center for Neurodegenerative Diseases.
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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, and Dominantly Inherited Alzheimer Network. Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's Disease. Nature Medicine, 2019; DOI: 10.1038/s41591-018-0304-3