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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.

Studying a mouse model of Alzheimer's disease, neuroscientists at the Technische Universitaet Muenchen (TUM) 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.

"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," said Professor Arthur Konnerth, a Carl von Linde Senior Fellow of the TUM Institute for Advanced Study and the lead researcher of the study.

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.

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.

"An important conclusion from this study 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," Konnerth said.

"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," he added.

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