The new research suggests that AD in its earliest stage already causes changes in CSF-levels of tau and amyloid-beta and that these changes are both the results of the build-up of the amyloid-beta protein in brain, which is characteristic for the disease.
This study opens new perspectives on the use of these mouse models in translational research say the senior authors of the study Mathias Jucker and Matthias Staufenbiel. In particular, in therapy trials of sporadic and familial AD the mouse models should be instrumental to predict the CSF changes in patients. They also could help to discover new early biomarkers in CSF and other bodily fluids.
Processes related to AD start at least 10 to 20 years before the onset of the first clinical symptoms. At the moment of diagnosis, the disease has already caused severe brain damage. Thus, there is a critical need to characterize this pre-clinical stage of the disease and to identify patients at risk well ahead of any clinical complaint. This is particularly crucial for early treatment aiming to stop the disease before the emergence of irreversible symptoms and signs. Biomarkers could act as reliable predictors and indicators of a disease process. They offer one of the most promising paths, when it comes to early AD-diagnosis. Biomarkers include proteins in blood or spinal fluid, genetic variations (mutations) or brain changes detectable by imaging.
Very early biomarkers in humans that show changes at least a decade before AD symptoms are noted, can be found in the cerebrospinal fluid (CSF). In the CSF the amyloid-beta protein is decreased while the tau protein is increased. The causes for these CSF changes have been largely speculative mainly because of the lack of useful animal models that also mimic these changes.
In order to tackle this point, the scientists first developed highly-sensitive methods to reliably assess amyloid-beta and tau in AD transgenic mice (these mice develop amyloid plaques, one hallmark of the Alzheimer’s pathology in the brain). Then, by assessing amyloid-beta and tau at different time points the authors could show that amyloid-beta goes down in the CSF after the first amyloid plaques appear in the brain and, remarkably, this decrease in amyloid-beta is followed by an increase in tau in the cerebrospinal fluid. The latter is notable, because the mice neither develop the second hallmark of AD pathology, namely the tau deposits, so called neurofibrillary tangles, nor global neuronal loss. Thus it is shown for the first time that the increase of tau in the CSF can occur independently of neurofibrillary tangles or frank neuron loss (as these do not occur in the mouse models used).Citation
Changes in amyloid-b and Tau in the cerebrospinal fluid of transgenic mice overexpressing amyloid precursor protein. Sci. Transl. Med. 5, 194rexx (2013)
Silke Jakobi | idw
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy