Researchers have discovered a way to better predict progression of Alzheimer's disease. By imaging microglial activation levels with positron emission tomography (PET), researchers were able to better predict progression of the disease than with beta-amyloid PET imaging, according to a study published in the April issue of the Journal of Nuclear Medicine.
According to the Alzheimer's Association, an estimated 5.3 million Americans are currently living with Alzheimer's disease. By 2025, that number is expected to increase to more than seven million.
Multimodal correlation analysis of cognitive testing with terminal PET and immunohistochemical results in PS2APP mice at study termination. Representative PET images (z score on MRI template), immunohistochemistry (fused methoxy-X04 [blue] and Iba1 [red]), and WM findings of individual mice, showing either low (orange) or high (magenta) markers of microglial activation at study termination.
Credit: Focke C, Blume T, Zott B, Shi Y, et al.
Usage Restrictions: Please give appropriate credit and indicate if changes were made.
The hallmark brain changes for those with Alzheimer's disease include the accumulation of beta-amyloid plaques. When microglial cells from the central nervous system recognize the presence of beta-amyloid plaques, they produce an inflammatory reaction in the brain.
"The 18-kD translocator protein (TSPO) is highly expressed in activated microglia, which makes it a valuable biomarker to assess inflammation in the brain," said Matthias Brendel, MD, MHBA, at Ludwig-Maximilians-University of Munich in Germany.
"In our study, we utilized TSPO-PET imaging to determine whether microglial activation had any influence on cognitive outcomes in an amyloid mouse model."
In the study, researchers compiled a series of PET images for 10 transgenic mice with beta-amyloid proteins and seven wild-type mice. TSPO PET imaging of activated microglia was conducted at eight, 9.5, 11.5 and 13 months, and beta-amyloid PET imaging was performed at eight and 13 months. Upon completion of the imaging, researchers then subjected the mice to a water maze in which the mice were to distinguish between a floating platform that would hold their weight and one that would sink.
The tasks were performed several times a day during a 1.5-week period. Memory performance in the water maze was assessed by measuring the average travel time from the start point to a platform each day of training and by calculating the traveled distance at the last day of training. After completing the water maze task, immunohistochemistry analyses were performed for microglia, amyloid and synaptic density.
Transgenic mice with the highest TSPO PET signal in the forebrain or other areas associated with spatial learning tended to have better cognitive performance in the water maze, while beta-amyloid signals in the same areas of the brain showed no correlation to cognitive outcomes in the maze.
Researchers found that an earlier microglial response to amyloid pathology in transgenic mice also protected synaptic density at follow-up. Specifically, transgenic mice with higher TSPO expression at eight months had much better cognitive outcomes in the water maze and higher synaptic density as confirmed by immunochemistry analyses.
"This study provides the first evidence that the level of microglial activation could be a far better predictor of current and future cognitive performance than beta-amyloid levels," noted Brendel.
"Keeping the limitations of mouse models in mind, it could be crucial to modify an individual's microglial activation state to ameliorate future cognitive decline. We believe that a balanced microglia activation is crucial for prevention of cognitive impairment."
The authors of "Early and Longitudinal Microglial Activation but Not Amyloid Accumulation Predicts Cognitive Outcome in PS2APP Mice" include Carola Focke, Maximilian Deussing, Claudio Schmidt, Simon Lindner, Franz-Josef Gildehaus, Leonie Beyer and Barbara von Ungern-Sternberg, Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany; Tanja Blume, Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany, and Center for Neuropathology and Prion Research, Ludwig-Maximilians-University of Munich, Munich, Germany; Benedikt Zott and Helmuth Adelsberger, Institute of Neuroscience, Technical University of Munich, Munich, Germany; Yuan Shi and Mario M. Dorostkar, Center for Neuropathology and Prion Research, Ludwig-Miximilians-University of Munich, Munich, Germany, and DZNE-German Center for Neurodegenerative Diseases, Munich, Germany; Finn Peters, DZNE-German Center for Neurodegenerative Diseases, Munich, Germany; Gernot Kleinberger, Munich Cluster for Systems Neurology, University of Munich, Munich, Germany, and Biomedical Center, Biochemistry, Ludwig-Maximilians-University of Munich, Munich, Germany; Peter Bartenstein and Matthias Brendel, Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany, and Munich Cluster for Systems Neurology, University of Munich, Munich, Germany; Laurence Ozmen and Karlheinz Baumann, Roche Pharma Research and Early Development, F. Hoffman-La Roche Ltd., Basel, Switzerland; Christian Haass, DZNE-German Center for Neurodegenerative Diseases, Munich, Germany, Munich Cluster for Systems Neurology, University of Munich, Munich, Germany, and Biomedical Center, Biochemistry, Ludwig-Maximilians-University of Munich, Munich, Germany; Jochen Herms, Center for Neuropathology and Prion Research, Ludwig-Maximilians-University of Munich, Munich, Germany, DZNE-German Center for Neurodegenerative Diseases, Munich, Germany, and Munich Cluster for Systems Neurology, University of Munich, Munich, Germany; Axel Rominger, Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany, Munich Cluster for Systems Neurology, University of Munich, Munich, Germany, and Department of Nuclear Medicine, Inselspital, University Hospital Bern, Bern, Switzerland.
This study was made available online in September 2018 ahead of final publication in print in April 2019.
For more information or to schedule an interview with the researchers, please contact Rebecca Maxey at (703) 652-6772 or firstname.lastname@example.org. Current and past issues of the Journal of Nuclear Medicine can be found online at http://jnm.
About the Society of Nuclear Medicine and Molecular Imaging
The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and medical organization dedicated to advancing nuclear medicine and molecular imaging, vital elements of precision medicine that allow diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes.
SNMMI's more than 17,000 members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings, and leading advocacy on key issues that affect molecular imaging and therapy research and practice.
For more information, visit http://www.
Rebecca Maxey | EurekAlert!
Bioengineers explore cardiac tissue remodeling after aortic valve replacement procedures
12.09.2019 | University of Colorado at Boulder
Gentle diagnosis of esophageal diseases
10.09.2019 | Leibniz-Institut für Photonische Technologien e. V.
Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Potsdam (both in Germany) and the University of Toronto (Canada) have pieced together a detailed time-lapse movie revealing all the major steps during the catalytic cycle of an enzyme. Surprisingly, the communication between the protein units is accomplished via a water-network akin to a string telephone. This communication is aligned with a ‘breathing’ motion, that is the expansion and contraction of the protein.
This time-lapse sequence of structures reveals dynamic motions as a fundamental element in the molecular foundations of biology.
Two research teams have succeeded simultaneously in measuring the long-sought Thorium nuclear transition, which enables extremely precise nuclear clocks. TU Wien (Vienna) is part of both teams.
If you want to build the most accurate clock in the world, you need something that "ticks" very fast and extremely precise. In an atomic clock, electrons are...
Researchers from Chalmers University of Technology have demonstrated a detector made from graphene that could revolutionize the sensors used in next-generation space telescopes. The findings were recently published in the scientific journal Nature Astronomy.
Beyond superconductors, there are few materials that can fulfill the requirements needed for making ultra-sensitive and fast terahertz (THz) detectors for...
A supersolid is a state of matter that can be described in simplified terms as being solid and liquid at the same time. In recent years, extensive efforts have been devoted to the detection of this exotic quantum matter. A research team led by Tilman Pfau and Tim Langen at the 5th Institute of Physics of the University of Stuttgart has succeeded in proving experimentally that the long-sought supersolid state of matter exists. The researchers report their results in Nature magazine.
In our everyday lives, we are familiar with matter existing in three different states: solid, liquid, or gas. However, if matter is cooled down to extremely...
A team headed by Prof. Steve Albrecht from the HZB will present a new world-record tandem solar cell at EU PVSEC, the world's largest international photovoltaic and solar energy conference and exhibition, in Marseille, France on September 11, 2019. This tandem solar cell combines the semiconducting materials perovskite and CIGS and achieves a certified efficiency of 23.26 per cent. One reason for this success lies in the cell’s intermediate layer of organic molecules: they self-organise to cover even rough semiconductor surfaces. Two patents have been filed for these layers.
Perovskite-based solar cells have experienced an incredibly rapid increase in efficiency over the last ten years. The combination of perovskites with classical...
10.09.2019 | Event News
04.09.2019 | Event News
29.08.2019 | Event News
13.09.2019 | Earth Sciences
13.09.2019 | Power and Electrical Engineering
13.09.2019 | Power and Electrical Engineering