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
Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University
Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
16.07.2018 | Physics and Astronomy
16.07.2018 | Life Sciences
16.07.2018 | Earth Sciences