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The researchers have discovered a way to better predict the evolution of Alzheimer's disease. By badyzing levels of microglial activation with positron emission tomography (PET), researchers were able to better predict the course of the disease than with PET imaging. beta-amyloid, according to a study published in the April issue of Journal of Nuclear Medicine.
According to the Alzheimer's Association, about 5.3 million Americans currently live with Alzheimer's disease. By the year 2025, this number is expected to reach more than seven million. The characteristic brain changes in people with Alzheimer's disease include the accumulation of beta-amyloid plaques. When microglial cells of the central nervous system recognize the presence of beta-amyloid plaques, they cause an inflammatory reaction in the brain.
"The 18 kD translocator protein (TSPO) is highly expressed in activated microglia, making it a valuable biomarker for badessing inflammation in the brain," said Matthias Brendel, MD, MHBA, of the Ludwig-Maximilians University Munich, Germany. "In our study, we used TSPO-PET imaging to determine whether microglial activation had an influence on cognitive outcomes in an amyloid mouse model."
As part of the study, the researchers compiled a series of PET images for 10 transgenic mice containing beta-amyloid proteins and seven wild-type mice. TSPO PET imaging of activated microglia was performed at eight, 9.5, 11.5, and 13 months, and beta-amyloid PET imaging at eight and 13 months. Once the imaging was complete, the researchers then subjected the mice to an aquatic labyrinth in which they had to distinguish between a floating platform that could support their weight and another that could sink. The tasks were done several times a day for a week and a half. Aquatic maze memory performance was badessed by measuring the average travel time between the starting point and a platform each training day and calculating the distance traveled on the last day of training. Once the water labyrinth task was completed, immunohistochemical badyzes were performed to determine the microglial, amyloid and synaptic density.
Transgenic mice with the highest PET TSPO signal in the forebrain or in other areas badociated with spatial learning tended to have better cognitive performance in the aquatic labyrinth, whereas Amyloids in the same areas of the brain showed no correlation with cognitive outcomes in the labyrinth. The researchers found that a prior microglial response to amyloid pathology in transgenic mice also protected synaptic density during follow-up. Specifically, transgenic mice with higher TSPO expression at eight months had much better cognitive results in the aquatic labyrinth and higher synaptic density, as confirmed by immunochemical badyzes.
"This study provides the first evidence that the level of microglial activation could be a much better predictor of current and future cognitive performance than beta-amyloid levels," noted Brendel. "Keeping in mind the limitations of murine models, it might be crucial to alter a person's microglial activation state to improve his or her future cognitive decline." think that a balanced activation of microglia is crucial for the prevention of cognitive disorders. "
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Material provided by Society of Nuclear Medicine and Molecular Imaging. Note: Content can be changed for style and length.
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