Years before symptoms of Alzheimer’s disease manifest, the brain starts changing and neurons are slowly degraded. Scientists at the German Center for Neurodegenerative Diseases (DZNE), the Hertie Institute for Clinical Brain Research (HIH) and the University Hospital Tübingen now show that a protein found in the blood can be used to precisely monitor disease progression long before first clinical signs appear. This blood marker offers new possibilities for testing therapies. The study was carried out in cooperation with an international research team and published in the journal “Nature Medicine”.
“The fact that there is still no effective treatment for Alzheimer’s is partly because current therapies start much too late,” says Mathias Jucker, a senior researcher at the DZNE’s Tübingen site and at the HIH. He headed the current study.
In order to develop better treatments, scientists therefore need reliable methods to monitor and predict the course of the disease before symptoms such as memory changes occur. A blood test is better suited for this than e. g. expensive brain scans.
Recently, there was some progress in the development of such blood tests. Most of them are based on so-called amyloid proteins. In Alzheimer’s disease, amyloid proteins accumulate in the brain and also occur in the blood. However, Jucker and his colleagues take a different approach. “Our blood test does not look at the amyloid, but at what it does in the brain, namely neurodegeneration. In other words, we look at the death of neurons,” says Jucker.
Traces in the bloodstream
When brain cells die, their remains can be detected in the blood. “Normally, however, such proteins are rapidly degraded in the blood and are therefore not very suitable as markers for a neurodegenerative disease,” explains Jucker. “An exception, however, is a small piece of so-called neurofilament that is surprisingly resistant to this degradation.”
The blood test of Jucker and colleagues is based on this protein. In the current study, the scientists show that neurofilament accumulates in the blood long before the onset of clinical symptoms (i.e. already during the so-called preclinical phase) and that it very sensitively reflects the course of the disease and enables predictions on future developments.
The study is based on data and samples from 405 individuals that were analyzed within an international research collaboration: the “Dominantly Inherited Alzheimer Network” (DIAN). In addition to the DZNE, the HIH and the University Hospital Tübingen, the Washington University School of Medicine in St. Louis (USA) and other institutions all over the world are involved.
This network investigates families in which Alzheimer’s disease already occurs in middle age due to certain gene variations. Genetic analyses allow very accurate predictions as to whether and when a family member will develop dementia.
Omens of dementia
Jucker and his colleagues monitored the development of neurofilament concentration in these individuals from year to year. Up to 16 years before the calculated onset of dementia symptoms, there were noticeable changes in the blood. “It is not the absolute neurofilament concentration, but its temporal evolution, which is meaningful and allows predictions about the future progression of the disease,” says Jucker.
In fact, in further investigations, the scientists showed that changes in neurofilament concentration reflect neuronal degradation very accurately and allow predictions on how brain damage will develop. “We were able to predict loss of brain mass and cognitive changes that actually occurred two years later,” says Jucker.
While it turned out that the rate of change in neurofilament concentration was closely linked to brain degradation, correlation with the deposition of toxic amyloid proteins was far less pronounced. This supports the assumption that although amyloid proteins are triggers of disease, neuronal degradation occurs independently.
A tool for therapy research
Neurofilaments accumulate in the blood not only in Alzheimer’s but also in the course of other neurodegenerative disorders. Thus, the test is only conditionally suitable for diagnosing Alzheimer’s. “However, the test accurately shows the course of the disease and is therefore a powerful instrument for investigating novel Alzheimer’s therapies in clinical trials,” says Jucker.
German Center for Neurodegenerative Diseases (DZNE)
Dr. Marcus Neitzert, Science Editor
Phone: +49 228 43302-267
Hertie Institute for Clinical Brain Research
Dr. Mareike Kardinal, Director of Communications
Phone: +49 7071 29-88800
University Hospital Tübingen
Claudia Löwe, Press Officer
Phone: +49 7071 29-81020
Preische O, Schultz SA, Apel A, et al. (2019): “Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s Disease”, Nature Medicine, DOI: 10.1038/s41591-018-0304-3
Dr. Marcus Neitzert | idw - Informationsdienst Wissenschaft
Infants later diagnosed with autism follow adults’ gaze, but seldom initiate joint attention
24.05.2019 | Schwedischer Forschungsrat - The Swedish Research Council
When wheels and heads are spinning - DFG research project on motion sickness in automated driving
22.05.2019 | Technische Universität Berlin
A new assessment of NASA's record of global temperatures revealed that the agency's estimate of Earth's long-term temperature rise in recent decades is accurate to within less than a tenth of a degree Fahrenheit, providing confidence that past and future research is correctly capturing rising surface temperatures.
The most complete assessment ever of statistical uncertainty within the GISS Surface Temperature Analysis (GISTEMP) data product shows that the annual values...
Physicists at the University of Basel are able to show for the first time how a single electron looks in an artificial atom. A newly developed method enables them to show the probability of an electron being present in a space. This allows improved control of electron spins, which could serve as the smallest information unit in a future quantum computer. The experiments were published in Physical Review Letters and the related theory in Physical Review B.
The spin of an electron is a promising candidate for use as the smallest information unit (qubit) of a quantum computer. Controlling and switching this spin or...
Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...
With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.
Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...
'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.
However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...
29.04.2019 | Event News
17.04.2019 | Event News
15.04.2019 | Event News
24.05.2019 | Physics and Astronomy
24.05.2019 | Medical Engineering
24.05.2019 | Life Sciences