Single-neuron observations mark steps in Alzheimer's disease
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
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. 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.
This schematic illustration shows the experimental arrangement for in vivo two-photon calcium imaging of stimulation-evoked neuronal activity in anesthetized mice. At left, in vivo two-photon image of the visual cortex. The neurons are stained with the calcium indicator dye Oregon Green BAPTA-1 (green, OGB-1) and the astrocytes with Sulforhodamine 101 (yellow, SR101). Right, visual stimuli were projected on a screen placed in front of the eye of the mouse. Credit: Konnerth lab, TU MuenchenUsing 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."
This is a table illustrating the staged decline of the cortical circuit function on the level of the beta-amyloid load, the behavioral deficits and the visual processing. Credit: Konnerth lab, TU MuenchenThe 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."
More information: Nature Communications, April 10, 2012. DOI: 10.1038/ncomms1783
Journal reference: Nature Communications
Provided by Technische Universitaet Muenchen
- Alzheimer's vaccine clears plaque but has little effect on learning and memory impairment Apr 04, 2008 | not rated yet | 0
- Imaging study reveals rapid formation of Alzheimer's-associated plaques Feb 06, 2008 | not rated yet | 0
- Epigenetic culprit in Alzheimer's memory decline Feb 29, 2012 | not rated yet | 0
- New method reveals how individual nerve cells process visual input Apr 29, 2010 | not rated yet | 0
- Alzheimer's-like brain changes found in cognitively normal elders with amyloid plaques Mar 30, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
The idea behind a reverse shock
2 hours ago So in a supernova explosion for example (5th slide) http://www.astro.princeton.edu/~burrows/classes/541/blastwavesChisari.pdf Ambient medium is...
Guass's Law for a charge distribution
2 hours ago First, this is not a homework question, just something I've been confused about for some time. I understand how to use Guass's law in many ways but...
3 hours ago Hello :) i'm new to this forum, so excuse me for my straightforwardness ;) I'm working on my bachelor work and i can't find a solution. I'm writing...
siphon and bernouli theorum
5 hours ago 1. I found this diagram on book but there weren't any description.can someone tell me, what its trying to tell specially by those two red lines...
Hot gas expansion rate into outer space
5 hours ago Good Morning Sirs, it seems to be surprisingly hard to get the numbers of a mystery: How fast expand hot rocket exhaust gases into empty space? ...
Magnetic field lines through copper
10 hours ago Hello. Assume an electron gun, as in CRT, made of plumbing copper instead of glass. Using magnetic scanning coils to move electron beam. Will the...
- More from Physics Forums - Classical Physics
More news stories
In the search for medication against Alzheimer's disease, scientists have focused – among other factors – on drugs that can break down Amyloid beta (A-beta). After all, it is the accumulation of A-beta that causes the ...
Alzheimer's disease & dementia May 24, 2013 | not rated yet | 0
(Medical Xpress)—The way Alzheimer's disease is portrayed by advocacy groups and the media is having undue influence on the euthanasia debate, according to a Deakin University nursing ethics professor.
Alzheimer's disease & dementia May 24, 2013 | not rated yet | 2
Cinnamon: Can the red-brown spice with the unmistakable fragrance and variety of uses offer an important benefit? The common baking spice might hold the key to delaying the onset of –– or warding off ...
Alzheimer's disease & dementia May 23, 2013 | 5 / 5 (5) | 0 |
An anti-cancer drug reverses memory deficits in an Alzheimer's disease mouse model, University of Pittsburgh Graduate School of Public Health researchers confirm in the journal Science.
Alzheimer's disease & dementia May 23, 2013 | not rated yet | 0 |
Teams of highly respected Alzheimer's researchers failed to replicate what appeared to be breakthrough results for the treatment of this brain disease when they were published last year in the journal Science.
Alzheimer's disease & dementia May 23, 2013 | 3 / 5 (2) | 3 |
(HealthDay)—Animals make great companions for senior citizens, but elderly people who always drive with a pet in the car are far more likely to crash than those who never drive with a pet, researchers have ...
32 minutes ago | not rated yet | 0
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
8 hours ago | 5 / 5 (2) | 5
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
8 hours ago | not rated yet | 1
Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...
8 hours ago | not rated yet | 0
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
8 hours ago | not rated yet | 0