Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Single-neuron observations mark steps in Alzheimer's disease

20.04.2012
Multiple disease-related changes progress in parallel through distinct stages

Studying a mouse model of Alzheimer's disease, neuroscientists at the Technische Universitaet Muenchen have observed correlations between increases in both soluble and plaque-forming beta-amyloid – a protein implicated in the disease process – and dysfunctional developments on several levels: individual cortical neurons, neuronal circuits, sensory cognition, and behavior.


These are microscopic images of a brain section (bottom: overview. top: enlarged view of the visual cortex), obtained from an APP23xPS45 Alzheimer mouse, in which the beta-amyloid plaques are labeled with Thioflavin-S. Credit: Konnerth lab, TU Muenchen

Their results, published in Nature Communications, show that these changes progress in parallel and that, together, they reveal distinct stages in Alzheimer's disease with a specific order in time.

In addition to its well known, devastating effects on memory and learning, Alzheimer's disease can also impair a person's sense of smell or vision. Typically these changes in sensory cognition only show themselves behaviorally when the disease is more advanced. A new study sheds light on what is happening in the brain throughout the disease process, specifically with respect to the part of the cerebral cortex responsible for integrating visual information. A team led by Prof. Arthur Konnerth, a Carl von Linde Senior Fellow of the TUM Institute for Advanced Study, has observed Alzheimer's-related changes in the visual cortex at the single-cell level.

Using a technique called two-photon calcium imaging, the researchers recorded both spontaneous and stimulated signaling activity in cortical neurons of living mice: transgenic mice carrying mutations that cause Alzheimer's disease in humans, and wild-type mice as a control group. By observing how neuronal signaling responded to a special kind of vision test – in which a simple grating pattern of light and dark bars moves in front of the mouse's eye – the scientists could characterize the visual circuit as being more or less "tuned" to specific orientations and directions of movement.

Konnerth explains, "Like many Alzheimer's patients, the diseased mice have impairments in their ability to discriminate visual objects. Our results provide important new insights on the cause that may underlie the impaired behavior, by identifying in the visual cortex a fraction of neurons with a strongly disturbed function." And within this group, the researchers discovered, there are two subsets of neurons – both dysfunctional, but in completely different ways. One subset, thought to be the first neurons to degenerate, showed no activity at all; the other showed a pathologically high level of activity, rendering these neurons incapable of properly sensing objects in the mouse's environment. "While around half of the neurons in the visual cortex were disturbed in one way or the other, roughly half responded normally," notes Christine Grienberger, a doctoral candidate in Konnerth's institute and first author of this paper. "That could have significant implications for future research in the field of Alzheimer's disease, as our findings raise the question of whether future work only needs to target this population of neurons that are disturbed in their function."

The in vivo single-neuron experiments were carried out for three age groups, corresponding to different stages of this progressive, degenerative disease. The results were correlated with other measurements, including soluble beta-amyloid levels and the density of beta-amyloid plaques in the brain tissue. The researchers' findings show for the first time a progressive decline of function in cortical circuits. "An important conclusion from this study," Konnerth says, "is that the Alzheimer's disease-related changes on all levels – including behavior, cortical circuit dysfunction, and the density of amyloid plaques in diseased brains – progress in parallel in a distinct temporal order. In the future, the identification of such stages in patients may help researchers pinpoint stage-specific and effective therapies, with reduced levels of side effects."

This research was supported by the German Excellence Initiative (TUM-IAS, CIPSM); the German Research Foundation (DFG, IRTG 1373); ERAnet; and the Friedrich Schiedel Foundation.

Original publication:
Staged decline of neuronal function in vivo in an animal model of Alzheimer's disease
Christine Grienberger, Nathalie L. Rochefort, Helmuth Adelsberger, Horst A. Henning, Daniel N. Hill, Julia Reichwald, Matthias Staufenbiel, and Arthur Konnerth
Nature Communications, April 10, 2012.
DOI: 10.1038/ncomms1783
Contact:
Prof. Arthur Konnerth
Institute for Neuroscience
Technische Universitaet Muenchen
Biedersteinerstr. 29, 80802 Munich, Germany
Tel.: +49 (0)89 4140 3351
E-Mail: arthur.konnerth@lrz.tum.de
Web: http://www.ifn.me.tum.de/new/konnerth.html
Technische Universitaet Muenchen (TUM) is one of Europe's leading universities. It has roughly 460 professors, 9000 academic and non-academic staff, and 31,000 students. It focuses on the engineering sciences, natural sciences, life sciences, medicine, and economic sciences. After winning numerous awards, it was selected as an "Elite University" in 2006 by the Science Council (Wissenschaftsrat) and the German Research Foundation (DFG). The university's global network includes an outpost with a research campus in Singapore. TUM is dedicated to the ideal of a top-level research-based entrepreneurial university.

Patrick Regan | EurekAlert!
Further information:
http://www.tum.de

More articles from Health and Medicine:

nachricht Inselspital: Fewer CT scans needed after cerebral bleeding
20.03.2019 | Universitätsspital Bern

nachricht Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New gene potentially involved in metastasis identified

Gene named after Roman goddess Minerva as immune cells get stuck in the fruit fly’s head

Cancers that display a specific combination of sugars, called T-antigen, are more likely to spread through the body and kill a patient. However, what regulates...

Im Focus: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Listening to the quantum vacuum

26.03.2019 | Physics and Astronomy

The struggle for life in the Dead Sea sediments: Necrophagy as a survival mechanism

26.03.2019 | Earth Sciences

Mangroves and their significance for climate protection

26.03.2019 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>